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

Ryan J. Smith, Hongpan Zhang, Shengen Shawn Hu, Theodora Yung, Roshane Francis, Lilian Lee, Mark W. Onaitis, Peter B. Dirks, Chongzhi Zang () and Tae-Hee Kim ()
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Ryan J. Smith: The Hospital for Sick Children
Hongpan Zhang: University of Virginia School of Medicine
Shengen Shawn Hu: University of Virginia School of Medicine
Theodora Yung: The Hospital for Sick Children
Roshane Francis: The Hospital for Sick Children
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
Chongzhi Zang: University of Virginia School of Medicine
Tae-Hee Kim: The Hospital for Sick Children

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30624-w

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DOI: 10.1038/s41467-022-30624-w

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