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Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.

Publication ,  Journal Article
Smith, RJ; Zhang, H; Hu, SS; Yung, T; Francis, R; Lee, L; Onaitis, MW; Dirks, PB; Zang, C; Kim, T-H
Published in: Nat Commun
May 26, 2022

Development of the gastrointestinal system occurs after gut tube closure, guided by spatial and temporal control of gene expression. However, it remains unclear what forces regulate these spatiotemporal gene expression patterns. Here we perform single-cell chromatin profiling of the primitive gut tube to reveal organ-specific chromatin patterns that reflect the anatomical patterns of distinct organs. We generate a comprehensive map of epigenomic changes throughout gut development, demonstrating that dynamic chromatin accessibility patterns associate with lineage-specific transcription factor binding events to regulate organ-specific gene expression. Additionally, we show that loss of Sox2 and Cdx2, foregut and hindgut lineage-specific transcription factors, respectively, leads to fate shifts in epigenomic patterns, linking transcription factor binding, chromatin accessibility, and lineage fate decisions in gut development. Notably, abnormal expression of Sox2 in the pancreas and intestine impairs lineage fate decisions in both development and adult homeostasis. Together, our findings define the chromatin and transcriptional mechanisms of organ identity and lineage plasticity in development and adult homeostasis.

Duke Scholars

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 26, 2022

Volume

13

Issue

1

Start / End Page

2965

Location

England

Related Subject Headings

  • Transcription Factors
  • Humans
  • Gastrula
  • Epigenomics
  • Endoderm
  • Chromatin
  • Adult
 

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Smith, R. J., Zhang, H., Hu, S. S., Yung, T., Francis, R., Lee, L., … Kim, T.-H. (2022). Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions. Nat Commun, 13(1), 2965. https://doi.org/10.1038/s41467-022-30624-w
Smith, Ryan J., Hongpan Zhang, Shengen Shawn Hu, Theodora Yung, Roshane Francis, Lilian Lee, Mark W. Onaitis, Peter B. Dirks, Chongzhi Zang, and Tae-Hee Kim. “Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.Nat Commun 13, no. 1 (May 26, 2022): 2965. https://doi.org/10.1038/s41467-022-30624-w.
Smith RJ, Zhang H, Hu SS, Yung T, Francis R, Lee L, et al. Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions. Nat Commun. 2022 May 26;13(1):2965.
Smith, Ryan J., et al. “Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.Nat Commun, vol. 13, no. 1, May 2022, p. 2965. Pubmed, doi:10.1038/s41467-022-30624-w.
Smith RJ, Zhang H, Hu SS, Yung T, Francis R, Lee L, Onaitis MW, Dirks PB, Zang C, Kim T-H. Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions. Nat Commun. 2022 May 26;13(1):2965.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 26, 2022

Volume

13

Issue

1

Start / End Page

2965

Location

England

Related Subject Headings

  • Transcription Factors
  • Humans
  • Gastrula
  • Epigenomics
  • Endoderm
  • Chromatin
  • Adult