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Chemically induced revitalization of damaged hepatocytes for regenerative liver repair

ABSTRACT: Chemically induced revitalization of damaged hepatocytes for regenerative liver repair

PROVIDER: PRJNA974861 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24682003_1.fastq.gz	Fastqsanger.gz
	SRR24682003_2.fastq.gz	Fastqsanger.gz
	SRR24682004_1.fastq.gz	Fastqsanger.gz
	SRR24682004_2.fastq.gz	Fastqsanger.gz
	SRR24682005_1.fastq.gz	Fastqsanger.gz

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Chemically induced revitalization of damaged hepatocytes for regenerative liver repair.

Project description:In prolonged liver injury, hepatocytes undergo partial identity loss with decreased regenerative capacity, resulting in liver failure. Here, we identified a five compound (5C) combination that could restore hepatocyte identity and reverse the damage-associated phenotype (e.g., dysfunction, senescence, epithelial to mesenchymal transition, growth arrest, and pro-inflammatory gene expression) in damaged hepatocytes (dHeps) from CCl4-induced mice with chronic liver injury, resembling a direct chemical reprogramming approach. Systemic administration of 5C in mice with chronic liver injury promoted hepatocyte regeneration, improved liver function, and ameliorated liver fibrosis. The hepatocyte-associated transcriptional networks were reestablished with chemical treatment as revealed by motif analysis of ATAC-seq, and a hepatocyte-enriched transcription factor, Foxa2, was found to be essential for hepatocyte revitalization. Overall, our findings indicate that the phenotype and transcriptional program of dHeps can be reprogrammed to generate functional and regenerative hepatocytes by using only small molecules, as an alternative approach to liver repair and regeneration.

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Chemically induced revitalization of damaged hepatocytes for regenerative liver repair

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-20 | GSE233085 | GEO

Chemical induction of hepatocyte revitalization in mouse hepatocytes [RNA-seq 2]

Project description:We examined how each chemical contributed to hepatocyte revitalization by removing each component of the 5C induction cocktail individually. We then compared deach chemical contributed to hepatocyte revitalization by removing each component of the 5C induction cocktail individually

2023-11-21 | GSE233082 | GEO

Chemical induction of hepatocyte revitalization in mouse hepatocytes [RNA-seq 1]

Project description:Chemical induction of hepatocyte revitalization in mouse hepatocytes [RNA-seq 1]

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Chemical induction of hepatocyte revitalization in mouse hepatocytes [RNA-seq 2]

Project description:Chemical induction of hepatocyte revitalization in mouse hepatocytes [RNA-seq 2]

| PRJNA974870 | ENA

Chemical induction of hepatocyte revitalization in injured human hepatocytes [RNA-seq 3]

Project description:Chemical induction of hepatocyte revitalization in injured human hepatocytes [RNA-seq 3]

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Conversion of terminally committed hepatocytes to culturable bipotent progenitor cells with regenerative capacity

Project description:A challenge for advancing approaches to liver regeneration is loss of functional differentiation capacity when hepatocyte progenitors are maintained in culture. Recent lineage-tracing studies have shown that mature hepatocytes (MHs) convert to an immature state during chronic liver injury, and we investigated whether this conversion could be recapitulated in vitro and if such converted cells could represent a source of expandable hepatocytes. We report that a cocktail of small molecules, Y-27632, A-83-01 and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus our study advances the goals of liver regenerative medicine. Transcriptomic analyses for freshly isolated MHs and cells cultured for the designated periods with or without YAC stimulation (Matrix 1). Transcriptomic analysis for CLiPs which underwent hepatic induction (Matrix 2). Transcriptomic comparison of hepatic inducibility between CLiPs at early passage and those at late passages (Matrix 3). Transcriptomic comparison between chimera-derived rat cells (designated as “2nd”) and primary rat MH-derived cells (designated as “1st”) (Matrix 4).

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ATAC-seq data for damaged hepatocytes treated by a 3C cocktail [ATAC-seq]

Project description:To better understand the mechanism by which 3C induced revitalization, we next conducted epigenetic analysis to identify differences in transcriptional regulation. ATAC-seq data revealed that hepatocyte-enriched TFs, such as Hnf4a, Hnf1b, Hhex, and Prox1, and genes associated with epithelial cell proliferation and liver development were located in loci with open chromatin, whereas markers associated with mesenchymal transition, cell cycle arrest, apoptosis and inflammation (e.g., Col1a1, Mmp2, Ccl28, CxCr4, Ncf2) were located in closed chromatin loci in the 3C group

2023-11-21 | GSE233080 | GEO

ATAC-seq data for damaged hepatocytes treated by a 3C cocktail [ATAC-seq]

Project description:ATAC-seq data for damaged hepatocytes treated by a 3C cocktail [ATAC-seq]

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Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair

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