Obligate role for Rock1 and Rock2 in adult stem cell viability and function
The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The R...
Ausführliche Beschreibung
Autor*in: |
Arivazhagan Sambandam [verfasserIn] Elaine Storm [verfasserIn] Helen Tauc [verfasserIn] Jason A. Hackney [verfasserIn] David Garfield [verfasserIn] Patrick Caplazi [verfasserIn] John Liu [verfasserIn] Juan Zhang [verfasserIn] Hua Zhang [verfasserIn] Jeff Duggan [verfasserIn] Surinder Jeet [verfasserIn] Sarah Gierke [verfasserIn] Patrick Chang [verfasserIn] Xiumin Wu [verfasserIn] Robert Newman [verfasserIn] Lucinda Tam [verfasserIn] Tuija Alcantar [verfasserIn] Lifen Wang [verfasserIn] Meron Roose-Girma [verfasserIn] Zora Modrusan [verfasserIn] Wyne P. Lee [verfasserIn] Heinrich Jasper [verfasserIn] Frederic de Sauvage [verfasserIn] Rajita Pappu [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
In: Heliyon - Elsevier, 2016, 9(2023), 3, Seite e14238- |
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Übergeordnetes Werk: |
volume:9 ; year:2023 ; number:3 ; pages:e14238- |
Links: |
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DOI / URN: |
10.1016/j.heliyon.2023.e14238 |
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Katalog-ID: |
DOAJ088551989 |
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520 | |a The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. | ||
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10.1016/j.heliyon.2023.e14238 doi (DE-627)DOAJ088551989 (DE-599)DOAJ5f0b411f56a24ccdae5dfc7e215eea4e DE-627 ger DE-627 rakwb eng Q1-390 H1-99 Arivazhagan Sambandam verfasserin aut Obligate role for Rock1 and Rock2 in adult stem cell viability and function 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. Rho kinases Stem cells Hematopoiesis Intestinal regeneration Cytokinesis Science (General) Social sciences (General) Elaine Storm verfasserin aut Helen Tauc verfasserin aut Jason A. Hackney verfasserin aut David Garfield verfasserin aut Patrick Caplazi verfasserin aut John Liu verfasserin aut Juan Zhang verfasserin aut Hua Zhang verfasserin aut Jeff Duggan verfasserin aut Surinder Jeet verfasserin aut Sarah Gierke verfasserin aut Patrick Chang verfasserin aut Xiumin Wu verfasserin aut Robert Newman verfasserin aut Lucinda Tam verfasserin aut Tuija Alcantar verfasserin aut Lifen Wang verfasserin aut Meron Roose-Girma verfasserin aut Zora Modrusan verfasserin aut Wyne P. Lee verfasserin aut Heinrich Jasper verfasserin aut Frederic de Sauvage verfasserin aut Rajita Pappu verfasserin aut In Heliyon Elsevier, 2016 9(2023), 3, Seite e14238- (DE-627)835893197 (DE-600)2835763-2 24058440 nnns volume:9 year:2023 number:3 pages:e14238- https://doi.org/10.1016/j.heliyon.2023.e14238 kostenfrei https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e kostenfrei http://www.sciencedirect.com/science/article/pii/S2405844023014457 kostenfrei https://doaj.org/toc/2405-8440 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2023 3 e14238- |
spelling |
10.1016/j.heliyon.2023.e14238 doi (DE-627)DOAJ088551989 (DE-599)DOAJ5f0b411f56a24ccdae5dfc7e215eea4e DE-627 ger DE-627 rakwb eng Q1-390 H1-99 Arivazhagan Sambandam verfasserin aut Obligate role for Rock1 and Rock2 in adult stem cell viability and function 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. Rho kinases Stem cells Hematopoiesis Intestinal regeneration Cytokinesis Science (General) Social sciences (General) Elaine Storm verfasserin aut Helen Tauc verfasserin aut Jason A. Hackney verfasserin aut David Garfield verfasserin aut Patrick Caplazi verfasserin aut John Liu verfasserin aut Juan Zhang verfasserin aut Hua Zhang verfasserin aut Jeff Duggan verfasserin aut Surinder Jeet verfasserin aut Sarah Gierke verfasserin aut Patrick Chang verfasserin aut Xiumin Wu verfasserin aut Robert Newman verfasserin aut Lucinda Tam verfasserin aut Tuija Alcantar verfasserin aut Lifen Wang verfasserin aut Meron Roose-Girma verfasserin aut Zora Modrusan verfasserin aut Wyne P. Lee verfasserin aut Heinrich Jasper verfasserin aut Frederic de Sauvage verfasserin aut Rajita Pappu verfasserin aut In Heliyon Elsevier, 2016 9(2023), 3, Seite e14238- (DE-627)835893197 (DE-600)2835763-2 24058440 nnns volume:9 year:2023 number:3 pages:e14238- https://doi.org/10.1016/j.heliyon.2023.e14238 kostenfrei https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e kostenfrei http://www.sciencedirect.com/science/article/pii/S2405844023014457 kostenfrei https://doaj.org/toc/2405-8440 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2023 3 e14238- |
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10.1016/j.heliyon.2023.e14238 doi (DE-627)DOAJ088551989 (DE-599)DOAJ5f0b411f56a24ccdae5dfc7e215eea4e DE-627 ger DE-627 rakwb eng Q1-390 H1-99 Arivazhagan Sambandam verfasserin aut Obligate role for Rock1 and Rock2 in adult stem cell viability and function 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. Rho kinases Stem cells Hematopoiesis Intestinal regeneration Cytokinesis Science (General) Social sciences (General) Elaine Storm verfasserin aut Helen Tauc verfasserin aut Jason A. Hackney verfasserin aut David Garfield verfasserin aut Patrick Caplazi verfasserin aut John Liu verfasserin aut Juan Zhang verfasserin aut Hua Zhang verfasserin aut Jeff Duggan verfasserin aut Surinder Jeet verfasserin aut Sarah Gierke verfasserin aut Patrick Chang verfasserin aut Xiumin Wu verfasserin aut Robert Newman verfasserin aut Lucinda Tam verfasserin aut Tuija Alcantar verfasserin aut Lifen Wang verfasserin aut Meron Roose-Girma verfasserin aut Zora Modrusan verfasserin aut Wyne P. Lee verfasserin aut Heinrich Jasper verfasserin aut Frederic de Sauvage verfasserin aut Rajita Pappu verfasserin aut In Heliyon Elsevier, 2016 9(2023), 3, Seite e14238- (DE-627)835893197 (DE-600)2835763-2 24058440 nnns volume:9 year:2023 number:3 pages:e14238- https://doi.org/10.1016/j.heliyon.2023.e14238 kostenfrei https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e kostenfrei http://www.sciencedirect.com/science/article/pii/S2405844023014457 kostenfrei https://doaj.org/toc/2405-8440 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2023 3 e14238- |
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10.1016/j.heliyon.2023.e14238 doi (DE-627)DOAJ088551989 (DE-599)DOAJ5f0b411f56a24ccdae5dfc7e215eea4e DE-627 ger DE-627 rakwb eng Q1-390 H1-99 Arivazhagan Sambandam verfasserin aut Obligate role for Rock1 and Rock2 in adult stem cell viability and function 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. Rho kinases Stem cells Hematopoiesis Intestinal regeneration Cytokinesis Science (General) Social sciences (General) Elaine Storm verfasserin aut Helen Tauc verfasserin aut Jason A. Hackney verfasserin aut David Garfield verfasserin aut Patrick Caplazi verfasserin aut John Liu verfasserin aut Juan Zhang verfasserin aut Hua Zhang verfasserin aut Jeff Duggan verfasserin aut Surinder Jeet verfasserin aut Sarah Gierke verfasserin aut Patrick Chang verfasserin aut Xiumin Wu verfasserin aut Robert Newman verfasserin aut Lucinda Tam verfasserin aut Tuija Alcantar verfasserin aut Lifen Wang verfasserin aut Meron Roose-Girma verfasserin aut Zora Modrusan verfasserin aut Wyne P. Lee verfasserin aut Heinrich Jasper verfasserin aut Frederic de Sauvage verfasserin aut Rajita Pappu verfasserin aut In Heliyon Elsevier, 2016 9(2023), 3, Seite e14238- (DE-627)835893197 (DE-600)2835763-2 24058440 nnns volume:9 year:2023 number:3 pages:e14238- https://doi.org/10.1016/j.heliyon.2023.e14238 kostenfrei https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e kostenfrei http://www.sciencedirect.com/science/article/pii/S2405844023014457 kostenfrei https://doaj.org/toc/2405-8440 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2023 3 e14238- |
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10.1016/j.heliyon.2023.e14238 doi (DE-627)DOAJ088551989 (DE-599)DOAJ5f0b411f56a24ccdae5dfc7e215eea4e DE-627 ger DE-627 rakwb eng Q1-390 H1-99 Arivazhagan Sambandam verfasserin aut Obligate role for Rock1 and Rock2 in adult stem cell viability and function 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. Rho kinases Stem cells Hematopoiesis Intestinal regeneration Cytokinesis Science (General) Social sciences (General) Elaine Storm verfasserin aut Helen Tauc verfasserin aut Jason A. Hackney verfasserin aut David Garfield verfasserin aut Patrick Caplazi verfasserin aut John Liu verfasserin aut Juan Zhang verfasserin aut Hua Zhang verfasserin aut Jeff Duggan verfasserin aut Surinder Jeet verfasserin aut Sarah Gierke verfasserin aut Patrick Chang verfasserin aut Xiumin Wu verfasserin aut Robert Newman verfasserin aut Lucinda Tam verfasserin aut Tuija Alcantar verfasserin aut Lifen Wang verfasserin aut Meron Roose-Girma verfasserin aut Zora Modrusan verfasserin aut Wyne P. Lee verfasserin aut Heinrich Jasper verfasserin aut Frederic de Sauvage verfasserin aut Rajita Pappu verfasserin aut In Heliyon Elsevier, 2016 9(2023), 3, Seite e14238- (DE-627)835893197 (DE-600)2835763-2 24058440 nnns volume:9 year:2023 number:3 pages:e14238- https://doi.org/10.1016/j.heliyon.2023.e14238 kostenfrei https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e kostenfrei http://www.sciencedirect.com/science/article/pii/S2405844023014457 kostenfrei https://doaj.org/toc/2405-8440 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2023 3 e14238- |
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Arivazhagan Sambandam @@aut@@ Elaine Storm @@aut@@ Helen Tauc @@aut@@ Jason A. Hackney @@aut@@ David Garfield @@aut@@ Patrick Caplazi @@aut@@ John Liu @@aut@@ Juan Zhang @@aut@@ Hua Zhang @@aut@@ Jeff Duggan @@aut@@ Surinder Jeet @@aut@@ Sarah Gierke @@aut@@ Patrick Chang @@aut@@ Xiumin Wu @@aut@@ Robert Newman @@aut@@ Lucinda Tam @@aut@@ Tuija Alcantar @@aut@@ Lifen Wang @@aut@@ Meron Roose-Girma @@aut@@ Zora Modrusan @@aut@@ Wyne P. Lee @@aut@@ Heinrich Jasper @@aut@@ Frederic de Sauvage @@aut@@ Rajita Pappu @@aut@@ |
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Arivazhagan Sambandam misc Q1-390 misc H1-99 misc Rho kinases misc Stem cells misc Hematopoiesis misc Intestinal regeneration misc Cytokinesis misc Science (General) misc Social sciences (General) Obligate role for Rock1 and Rock2 in adult stem cell viability and function |
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Obligate role for Rock1 and Rock2 in adult stem cell viability and function |
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Arivazhagan Sambandam Elaine Storm Helen Tauc Jason A. Hackney David Garfield Patrick Caplazi John Liu Juan Zhang Hua Zhang Jeff Duggan Surinder Jeet Sarah Gierke Patrick Chang Xiumin Wu Robert Newman Lucinda Tam Tuija Alcantar Lifen Wang Meron Roose-Girma Zora Modrusan Wyne P. Lee Heinrich Jasper Frederic de Sauvage Rajita Pappu |
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obligate role for rock1 and rock2 in adult stem cell viability and function |
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Obligate role for Rock1 and Rock2 in adult stem cell viability and function |
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The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. |
abstractGer |
The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. |
abstract_unstemmed |
The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems. |
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Obligate role for Rock1 and Rock2 in adult stem cell viability and function |
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https://doi.org/10.1016/j.heliyon.2023.e14238 https://doaj.org/article/5f0b411f56a24ccdae5dfc7e215eea4e http://www.sciencedirect.com/science/article/pii/S2405844023014457 https://doaj.org/toc/2405-8440 |
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Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. 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