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

Publication ,  Journal Article
Chen, T; Oh, S; Gregory, S; Shen, X; Diehl, AM
Published in: JCI Insight
November 19, 2020

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 factors regulated by those pathways.

Duke Scholars

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

November 19, 2020

Volume

5

Issue

22

Location

United States

Related Subject Headings

  • Single-Cell Analysis
  • Signal Transduction
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Regeneration
  • Liver
  • Hepatocytes
  • Cell Proliferation
  • Biomarkers
 

Citation

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Chen, T., Oh, S., Gregory, S., Shen, X., & Diehl, A. M. (2020). Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration. JCI Insight, 5(22). https://doi.org/10.1172/jci.insight.141024
Chen, Tianyi, Sehhoon Oh, Simon Gregory, Xiling Shen, and Anna Mae Diehl. “Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.JCI Insight 5, no. 22 (November 19, 2020). https://doi.org/10.1172/jci.insight.141024.
Chen T, Oh S, Gregory S, Shen X, Diehl AM. Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration. JCI Insight. 2020 Nov 19;5(22).
Chen, Tianyi, et al. “Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.JCI Insight, vol. 5, no. 22, Nov. 2020. Pubmed, doi:10.1172/jci.insight.141024.
Chen T, Oh S, Gregory S, Shen X, Diehl AM. Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration. JCI Insight. 2020 Nov 19;5(22).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

November 19, 2020

Volume

5

Issue

22

Location

United States

Related Subject Headings

  • Single-Cell Analysis
  • Signal Transduction
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Regeneration
  • Liver
  • Hepatocytes
  • Cell Proliferation
  • Biomarkers