Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary

Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and...
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Autor*in:	Nobukatsu Horita [verfasserIn] Theresa M. Keeley [verfasserIn] Elise S. Hibdon [verfasserIn] Elizabeth Delgado [verfasserIn] Daniel Lafkas [verfasserIn] Christian W. Siebel [verfasserIn] Linda C. Samuelson [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells

Übergeordnetes Werk:	In: Cellular and Molecular Gastroenterology and Hepatology - Elsevier, 2017, 13(2022), 1, Seite 275-287
Übergeordnetes Werk:	volume:13 ; year:2022 ; number:1 ; pages:275-287

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.jcmgh.2021.08.012

Katalog-ID:	DOAJ048789577

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520			\|a Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis.
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650		4	\|a Gastric Organoids
650		4	\|a Notch Inhibitory Antibodies
650		4	\|a LGR5 Stem Cells
653		0	\|a Diseases of the digestive system. Gastroenterology
700	0		\|a Theresa M. Keeley \|e verfasserin \|4 aut
700	0		\|a Elise S. Hibdon \|e verfasserin \|4 aut
700	0		\|a Elizabeth Delgado \|e verfasserin \|4 aut
700	0		\|a Daniel Lafkas \|e verfasserin \|4 aut
700	0		\|a Christian W. Siebel \|e verfasserin \|4 aut
700	0		\|a Linda C. Samuelson \|e verfasserin \|4 aut
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publishDate	2022
allfields	10.1016/j.jcmgh.2021.08.012 doi (DE-627)DOAJ048789577 (DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447 DE-627 ger DE-627 rakwb eng RC799-869 Nobukatsu Horita verfasserin aut Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis. Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology Theresa M. Keeley verfasserin aut Elise S. Hibdon verfasserin aut Elizabeth Delgado verfasserin aut Daniel Lafkas verfasserin aut Christian W. Siebel verfasserin aut Linda C. Samuelson verfasserin aut In Cellular and Molecular Gastroenterology and Hepatology Elsevier, 2017 13(2022), 1, Seite 275-287 (DE-627)823790088 (DE-600)2819778-1 2352345X nnns volume:13 year:2022 number:1 pages:275-287 https://doi.org/10.1016/j.jcmgh.2021.08.012 kostenfrei https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352345X2100179X kostenfrei https://doaj.org/toc/2352-345X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 1 275-287
spelling	10.1016/j.jcmgh.2021.08.012 doi (DE-627)DOAJ048789577 (DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447 DE-627 ger DE-627 rakwb eng RC799-869 Nobukatsu Horita verfasserin aut Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis. Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology Theresa M. Keeley verfasserin aut Elise S. Hibdon verfasserin aut Elizabeth Delgado verfasserin aut Daniel Lafkas verfasserin aut Christian W. Siebel verfasserin aut Linda C. Samuelson verfasserin aut In Cellular and Molecular Gastroenterology and Hepatology Elsevier, 2017 13(2022), 1, Seite 275-287 (DE-627)823790088 (DE-600)2819778-1 2352345X nnns volume:13 year:2022 number:1 pages:275-287 https://doi.org/10.1016/j.jcmgh.2021.08.012 kostenfrei https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352345X2100179X kostenfrei https://doaj.org/toc/2352-345X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 1 275-287
allfields_unstemmed	10.1016/j.jcmgh.2021.08.012 doi (DE-627)DOAJ048789577 (DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447 DE-627 ger DE-627 rakwb eng RC799-869 Nobukatsu Horita verfasserin aut Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis. Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology Theresa M. Keeley verfasserin aut Elise S. Hibdon verfasserin aut Elizabeth Delgado verfasserin aut Daniel Lafkas verfasserin aut Christian W. Siebel verfasserin aut Linda C. Samuelson verfasserin aut In Cellular and Molecular Gastroenterology and Hepatology Elsevier, 2017 13(2022), 1, Seite 275-287 (DE-627)823790088 (DE-600)2819778-1 2352345X nnns volume:13 year:2022 number:1 pages:275-287 https://doi.org/10.1016/j.jcmgh.2021.08.012 kostenfrei https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352345X2100179X kostenfrei https://doaj.org/toc/2352-345X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 1 275-287
allfieldsGer	10.1016/j.jcmgh.2021.08.012 doi (DE-627)DOAJ048789577 (DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447 DE-627 ger DE-627 rakwb eng RC799-869 Nobukatsu Horita verfasserin aut Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis. Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology Theresa M. Keeley verfasserin aut Elise S. Hibdon verfasserin aut Elizabeth Delgado verfasserin aut Daniel Lafkas verfasserin aut Christian W. Siebel verfasserin aut Linda C. Samuelson verfasserin aut In Cellular and Molecular Gastroenterology and Hepatology Elsevier, 2017 13(2022), 1, Seite 275-287 (DE-627)823790088 (DE-600)2819778-1 2352345X nnns volume:13 year:2022 number:1 pages:275-287 https://doi.org/10.1016/j.jcmgh.2021.08.012 kostenfrei https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352345X2100179X kostenfrei https://doaj.org/toc/2352-345X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 1 275-287
allfieldsSound	10.1016/j.jcmgh.2021.08.012 doi (DE-627)DOAJ048789577 (DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447 DE-627 ger DE-627 rakwb eng RC799-869 Nobukatsu Horita verfasserin aut Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis. Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology Theresa M. Keeley verfasserin aut Elise S. Hibdon verfasserin aut Elizabeth Delgado verfasserin aut Daniel Lafkas verfasserin aut Christian W. Siebel verfasserin aut Linda C. Samuelson verfasserin aut In Cellular and Molecular Gastroenterology and Hepatology Elsevier, 2017 13(2022), 1, Seite 275-287 (DE-627)823790088 (DE-600)2819778-1 2352345X nnns volume:13 year:2022 number:1 pages:275-287 https://doi.org/10.1016/j.jcmgh.2021.08.012 kostenfrei https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352345X2100179X kostenfrei https://doaj.org/toc/2352-345X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 1 275-287
language	English
source	In Cellular and Molecular Gastroenterology and Hepatology 13(2022), 1, Seite 275-287 volume:13 year:2022 number:1 pages:275-287
sourceStr	In Cellular and Molecular Gastroenterology and Hepatology 13(2022), 1, Seite 275-287 volume:13 year:2022 number:1 pages:275-287
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells Diseases of the digestive system. Gastroenterology
isfreeaccess_bool	true
container_title	Cellular and Molecular Gastroenterology and Hepatology
authorswithroles_txt_mv	Nobukatsu Horita @@aut@@ Theresa M. Keeley @@aut@@ Elise S. Hibdon @@aut@@ Elizabeth Delgado @@aut@@ Daniel Lafkas @@aut@@ Christian W. Siebel @@aut@@ Linda C. Samuelson @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	823790088
id	DOAJ048789577
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ048789577</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230503010619.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2022 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.jcmgh.2021.08.012</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ048789577</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC799-869</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Nobukatsu Horita</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. 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callnumber-first	R - Medicine
author	Nobukatsu Horita
spellingShingle	Nobukatsu Horita misc RC799-869 misc Notch Signaling misc Stem Cell Niche misc Gastric Organoids misc Notch Inhibitory Antibodies misc LGR5 Stem Cells misc Diseases of the digestive system. Gastroenterology Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary
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topic_title	RC799-869 Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary Notch Signaling Stem Cell Niche Gastric Organoids Notch Inhibitory Antibodies LGR5 Stem Cells
topic	misc RC799-869 misc Notch Signaling misc Stem Cell Niche misc Gastric Organoids misc Notch Inhibitory Antibodies misc LGR5 Stem Cells misc Diseases of the digestive system. Gastroenterology
topic_unstemmed	misc RC799-869 misc Notch Signaling misc Stem Cell Niche misc Gastric Organoids misc Notch Inhibitory Antibodies misc LGR5 Stem Cells misc Diseases of the digestive system. Gastroenterology
topic_browse	misc RC799-869 misc Notch Signaling misc Stem Cell Niche misc Gastric Organoids misc Notch Inhibitory Antibodies misc LGR5 Stem Cells misc Diseases of the digestive system. Gastroenterology
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title	Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary
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title_full	Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary
author_sort	Nobukatsu Horita
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author_browse	Nobukatsu Horita Theresa M. Keeley Elise S. Hibdon Elizabeth Delgado Daniel Lafkas Christian W. Siebel Linda C. Samuelson
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title_sort	delta-like 1–expressing cells at the gland base promote proliferation of gastric antral stem cells in mousesummary
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title_auth	Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary
abstract	Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis.
abstractGer	Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis.
abstract_unstemmed	Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis.
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title_short	Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary
url	https://doi.org/10.1016/j.jcmgh.2021.08.012 https://doaj.org/article/c9c7c90acdba43d3b35b4515ca88e447 http://www.sciencedirect.com/science/article/pii/S2352345X2100179X https://doaj.org/toc/2352-345X
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up_date	2024-07-03T19:41:56.982Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ048789577</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230503010619.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2022 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.jcmgh.2021.08.012</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ048789577</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc9c7c90acdba43d3b35b4515ca88e447</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC799-869</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Nobukatsu Horita</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background & Aims: Notch pathway signaling maintains gastric epithelial cell homeostasis by regulating stem cell proliferation and differentiation. We previously identified NOTCH1 and NOTCH2 as the key Notch receptors controlling gastric stem cell function. Here, we identify the niche cells and critical Notch ligand responsible for regulating stem cell proliferation in the distal mouse stomach. Methods: Expression of Notch ligands in the gastric antrum was determined by quantitative reverse-transcriptase polymerase chain reaction and cellular localization was determined by in situ hybridization and immunostaining. The contribution of specific Notch ligands to regulate epithelial cell proliferation in adult mice was determined by inducible gene deletion, or by pharmacologic inhibition using antibodies directed against specific Notch ligands. Mouse gastric organoid cultures were used to confirm that Notch ligand signaling was epithelial specific. Results: Delta-like 1 (DLL1) and Jagged 1 (JAG1) were the most abundantly expressed Notch ligands in the adult mouse stomach, with DLL1 restricted to the antral gland base and JAG1 localized to the upper gland region. Inhibition of DLL1 alone or in combination with other Notch ligands significantly reduced epithelial cell proliferation and the growth of gastric antral organoids, while inhibition of the other Notch ligands, DLL4, JAG1, and JAG2, did not affect proliferation or organoid growth. Similarly, DLL1, and not DLL4, regulated proliferation of LGR5+ antral stem cells, which express the NOTCH1 receptor. Conclusions: DLL1 is the key Notch ligand regulating epithelial cell proliferation in the gastric antrum. We propose that DLL1-expressing cells at the gland base are Notch niche cells that signal to adjacent LGR5+ antral stem cells to regulate stem cell proliferation and epithelial homeostasis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Notch Signaling</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Stem Cell Niche</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gastric Organoids</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Notch Inhibitory Antibodies</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LGR5 Stem Cells</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the digestive system. Gastroenterology</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Theresa M. 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Delta-like 1–Expressing Cells at the Gland Base Promote Proliferation of Gastric Antral Stem Cells in MouseSummary

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