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

Author

Listed:
  • Ryan J. Smith

    (The Hospital for Sick Children
    University of Toronto)

  • Hongpan Zhang

    (University of Virginia School of Medicine
    University of Virginia)

  • Shengen Shawn Hu

    (University of Virginia School of Medicine)

  • Theodora Yung

    (The Hospital for Sick Children
    University of Toronto)

  • Roshane Francis

    (The Hospital for Sick Children
    University of Toronto)

  • Lilian Lee

    (The Hospital for Sick Children)

  • Mark W. Onaitis

    (University of California San Diego Medical Center)

  • Peter B. Dirks

    (The Hospital for Sick Children
    University of Toronto)

  • Chongzhi Zang

    (University of Virginia School of Medicine
    University of Virginia
    University of Virginia)

  • Tae-Hee Kim

    (The Hospital for Sick Children
    University of Toronto)

Abstract

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.

Suggested Citation

  • Ryan J. Smith & Hongpan Zhang & Shengen Shawn Hu & Theodora Yung & Roshane Francis & Lilian Lee & Mark W. Onaitis & Peter B. Dirks & Chongzhi Zang & Tae-Hee Kim, 2022. "Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30624-w
    DOI: 10.1038/s41467-022-30624-w
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    1. Lu Han & Praneet Chaturvedi & Keishi Kishimoto & Hiroyuki Koike & Talia Nasr & Kentaro Iwasawa & Kirsten Giesbrecht & Phillip C. Witcher & Alexandra Eicher & Lauren Haines & Yarim Lee & John M. Shanno, 2020. "Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Jean-Leon Chong & Pamela L. Wenzel & M. Teresa Sáenz-Robles & Vivek Nair & Antoney Ferrey & John P. Hagan & Yorman M. Gomez & Nidhi Sharma & Hui-Zi Chen & Madhu Ouseph & Shu-Huei Wang & Prashant Trikh, 2009. "E2f1–3 switch from activators in progenitor cells to repressors in differentiating cells," Nature, Nature, vol. 462(7275), pages 930-934, December.
    3. Sonja Nowotschin & Manu Setty & Ying-Yi Kuo & Vincent Liu & Vidur Garg & Roshan Sharma & Claire S. Simon & Nestor Saiz & Rui Gardner & Stéphane C. Boutet & Deanna M. Church & Pamela A. Hoodless & Anna, 2019. "The emergent landscape of the mouse gut endoderm at single-cell resolution," Nature, Nature, vol. 569(7756), pages 361-367, May.
    4. Ronan Russell & Phichitpol P. Carnese & Thomas G. Hennings & Emily M. Walker & Holger A. Russ & Jennifer S. Liu & Simone Giacometti & Roland Stein & Matthias Hebrok, 2020. "Loss of the transcription factor MAFB limits β-cell derivation from human PSCs," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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    1. Shengen Shawn Hu & Lin Liu & Qi Li & Wenjing Ma & Michael J. Guertin & Clifford A. Meyer & Ke Deng & Tingting Zhang & Chongzhi Zang, 2022. "Intrinsic bias estimation for improved analysis of bulk and single-cell chromatin accessibility profiles using SELMA," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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