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

JCI Insight
Tianyi ChenAnna Mae Diehl

Abstract

Adult liver has enormous regenerative capacity; 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-Seq to map state transitions in approximately 13,000 hepatocytes at single-cell resolution as livers regenerated, and validated key findings with IHC, 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, whereas 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 facto...Continue Reading

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Citations

Mar 24, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tianyi Chen, Anna Mae Diehl
Jun 4, 2021·Nature Reviews. Molecular Cell Biology·Lara CampanaStuart Forbes
Aug 7, 2021·Genes·Bhavani P MadakashiraKirsten C Sadler
Aug 28, 2021·International Journal of Molecular Sciences·Nicolas JacquelotPamela S Ohashi

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Datasets Mentioned

BETA
GSE158864
GSE158865
GSE158866
GSE158873

Methods Mentioned

BETA
RNA-Seq
RNA seq
scRNA-Seq
GTPase
ATAC-Seq
PCR

Software Mentioned

AUCell
ArchR
MACS2
Cicero
cisTopic
Bowtie2
ChromVAR
GSEA
Cell Ranger
UMAP

Related Concepts

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