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Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE158874 | GEO | 2020/10/02

REPOSITORIES: GEO

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Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scATAC-Seq]

Project description:Adult liver has enormous regenerative capacity as it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ function is unknown, but essential to prevent liver failure. Using partial hepatectomy (PHx) in mice to model liver regeneration, we integrated single-cell RNA and ATAC sequencing to map state transitions in ~ 13,000 hepatocytes at single-cell resolution as livers regenerated, and validated key findings with immunohistochemistry, to uncover how the organ regenerates hepatocytes while simultaneously fulfilling its vital tissue-specific functions. After PHx, hepatocytes rapidly and transiently diversified into multiple distinct populations with distinct functional bifurcation: some retained the chromatin landscapes and transcriptomes of hepatocytes in undamaged adult livers while others transitioned to acquire chromatin landscapes and transcriptomes of fetal hepatocytes. Injury-related signaling pathways known to be critical for regeneration were activated in transitioning hepatocytes and the most fetal-like hepatocytes exhibited chromatin landscapes that were enriched with transcription factors regulated by those pathways.

2020-10-02 | GSE158873 | GEO

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scRNA-Seq]

2020-10-02 | GSE158866 | GEO

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [ATAC-Seq]

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Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [RNA-Seq]

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Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration

Project description:Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration

| PRJNA666797 | ENA

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [RNA-Seq]

Project description:Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [RNA-Seq]

| PRJNA666787 | ENA

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [ATAC-Seq]

Project description:Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [ATAC-Seq]

| PRJNA666788 | ENA

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scRNA-Seq]

Project description:Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scRNA-Seq]

| PRJNA666791 | ENA

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scATAC-Seq]

Project description:Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration [scATAC-Seq]

| PRJNA666800 | ENA

In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration.

Project description:The identity of cellular populations that drive liver regeneration after injury is the subject of intense study, and the contributions of polyploid hepatocytes to organ regeneration and homeostasis have not been systematically assessed. Here, we developed a multicolor reporter allele system to genetically label and trace polyploid cells in situ. Multicolored polyploid hepatocytes undergo ploidy reduction and subsequent re-polyploidization after transplantation, providing direct evidence of the hepatocyte ploidy conveyor model. Marker segregation revealed that ploidy reduction rarely involves chromosome missegregation in vivo. We also traced polyploid hepatocytes in several different liver injury models and found robust proliferation in all settings. Importantly, ploidy reduction was seen in all injury models studied. We therefore conclude that polyploid hepatocytes have extensive regenerative capacity in situ and routinely undergo reductive mitoses during regenerative responses.

| S-EPMC7204404 | biostudies-literature

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