Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro

Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied sing...
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Autor*in:	Hua Wang [verfasserIn] Shaoping Zheng [verfasserIn] Hongbo Jiang [verfasserIn] Xuejia Wang [verfasserIn] Fengqin Zhou [verfasserIn] Zhihong Weng [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing

Übergeordnetes Werk:	In: Journal of Translational Medicine - BMC, 2003, 20(2022), 1, Seite 13
Übergeordnetes Werk:	volume:20 ; year:2022 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12967-022-03263-4

Katalog-ID:	DOAJ047843845

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520			\|a Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.
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allfields	10.1186/s12967-022-03263-4 doi (DE-627)DOAJ047843845 (DE-599)DOAJ40c7d1d1e6f641f4ac3e82b39a325433 DE-627 ger DE-627 rakwb eng Hua Wang verfasserin aut Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases. Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing Medicine R Shaoping Zheng verfasserin aut Hongbo Jiang verfasserin aut Xuejia Wang verfasserin aut Fengqin Zhou verfasserin aut Zhihong Weng verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 kostenfrei https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/toc/1479-5876 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13
spelling	10.1186/s12967-022-03263-4 doi (DE-627)DOAJ047843845 (DE-599)DOAJ40c7d1d1e6f641f4ac3e82b39a325433 DE-627 ger DE-627 rakwb eng Hua Wang verfasserin aut Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases. Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing Medicine R Shaoping Zheng verfasserin aut Hongbo Jiang verfasserin aut Xuejia Wang verfasserin aut Fengqin Zhou verfasserin aut Zhihong Weng verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 kostenfrei https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/toc/1479-5876 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13
allfields_unstemmed	10.1186/s12967-022-03263-4 doi (DE-627)DOAJ047843845 (DE-599)DOAJ40c7d1d1e6f641f4ac3e82b39a325433 DE-627 ger DE-627 rakwb eng Hua Wang verfasserin aut Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases. Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing Medicine R Shaoping Zheng verfasserin aut Hongbo Jiang verfasserin aut Xuejia Wang verfasserin aut Fengqin Zhou verfasserin aut Zhihong Weng verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 kostenfrei https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/toc/1479-5876 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13
allfieldsGer	10.1186/s12967-022-03263-4 doi (DE-627)DOAJ047843845 (DE-599)DOAJ40c7d1d1e6f641f4ac3e82b39a325433 DE-627 ger DE-627 rakwb eng Hua Wang verfasserin aut Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases. Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing Medicine R Shaoping Zheng verfasserin aut Hongbo Jiang verfasserin aut Xuejia Wang verfasserin aut Fengqin Zhou verfasserin aut Zhihong Weng verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 kostenfrei https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/toc/1479-5876 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13
allfieldsSound	10.1186/s12967-022-03263-4 doi (DE-627)DOAJ047843845 (DE-599)DOAJ40c7d1d1e6f641f4ac3e82b39a325433 DE-627 ger DE-627 rakwb eng Hua Wang verfasserin aut Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases. Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing Medicine R Shaoping Zheng verfasserin aut Hongbo Jiang verfasserin aut Xuejia Wang verfasserin aut Fengqin Zhou verfasserin aut Zhihong Weng verfasserin aut In Journal of Translational Medicine BMC, 2003 20(2022), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:20 year:2022 number:1 pages:13 https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 kostenfrei https://doi.org/10.1186/s12967-022-03263-4 kostenfrei https://doaj.org/toc/1479-5876 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 13
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Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Liver fibrosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hepatic stellate cell</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single-cell RNA sequencing</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shaoping Zheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield 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author	Hua Wang
spellingShingle	Hua Wang misc Liver fibrosis misc Hepatic stellate cell misc Single-cell RNA sequencing misc Medicine misc R Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
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topic_title	Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro Liver fibrosis Hepatic stellate cell Single-cell RNA sequencing
topic	misc Liver fibrosis misc Hepatic stellate cell misc Single-cell RNA sequencing misc Medicine misc R
topic_unstemmed	misc Liver fibrosis misc Hepatic stellate cell misc Single-cell RNA sequencing misc Medicine misc R
topic_browse	misc Liver fibrosis misc Hepatic stellate cell misc Single-cell RNA sequencing misc Medicine misc R
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title	Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
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title_full	Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
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author_browse	Hua Wang Shaoping Zheng Hongbo Jiang Xuejia Wang Fengqin Zhou Zhihong Weng
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title_sort	single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
title_auth	Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
abstract	Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.
abstractGer	Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.
abstract_unstemmed	Abstract Background The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. Methods We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. Results A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Conclusion Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.
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title_short	Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro
url	https://doi.org/10.1186/s12967-022-03263-4 https://doaj.org/article/40c7d1d1e6f641f4ac3e82b39a325433 https://doaj.org/toc/1479-5876
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author2	Shaoping Zheng Hongbo Jiang Xuejia Wang Fengqin Zhou Zhihong Weng
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up_date	2024-07-03T14:29:23.471Z
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Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). 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Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro

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