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

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

PROVIDER: PRJNA666787 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12755858.fastq.gz	Fastqsanger.gz
	SRR12755859.fastq.gz	Fastqsanger.gz
	SRR12755860.fastq.gz	Fastqsanger.gz
	SRR12755861.fastq.gz	Fastqsanger.gz
	SRR12755862.fastq.gz	Fastqsanger.gz

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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

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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]

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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]

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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

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]

2020-10-02 | GSE158865 | GEO

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

2020-10-02 | GSE158864 | GEO

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

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

2020-10-02 | GSE158874 | GEO

Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury

Project description:We aimed at elucidating the molecular and cellular crosstalk how inflammation controls proper liver regeneration. Therefore populations of liver macrophages were studied in genetically different mouse models after PHx using flow cytometry and single cell sequencing. Intercellular communication was examined in vitro, combining proteomics and transcriptomics. We observed marked changes in the composition of macrophage populations in the liver during the regeneration process. A F4/80+/CD11bhigh/CD14high macrophage population that is recruited in a CCR2 dependent manner increased rapidly after PHx. The polarization of the recruited macrophages differs from that under homeostatic conditions , but reappears during the late phase of the process. Proteomics, secretomics, and transcriptomics show that hepatocyte derived signals reduce the availability of active TGFb and thereby affect macrophage polarization and function towards the aforementioned phenotype. Depleting the TGFb type II receptor in myeloid cells phenocopies the hepatocyte-mediated macrophage polarization in vitro and in vivo. Moreover, disrupting TGFb signal transduction in macrophages is associated with increased expression of regeneration-relevant cytokines such as IL-6, reduced resection-induced liver damage and prolongated proliferation phase of hepatocytes in mice. Conclusion: Upon liver injury, hepatocytes have a major influence on the activation state of recruited liver macrophages by regulating the availability of active TGFb and TGFb induces a macrophage phenotype that aggravates injury. Ultimately, this mechanism influences the extent of intervention-induced liver injury as well as the proliferation phase during liver regeneration. In this data set, we investigated the influence of hepatocytes on co-cultured macrophages and vice versa.

2023-07-06 | GSE201467 | GEO

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