Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis

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. Shannon, Mitsuru Morimoto, James M. Wells, Takanori Takebe and Aaron M. Zorn ()
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Lu Han: University of Cincinnati, College of Medicine
Praneet Chaturvedi: University of Cincinnati, College of Medicine
Keishi Kishimoto: University of Cincinnati, College of Medicine
Hiroyuki Koike: University of Cincinnati, College of Medicine
Talia Nasr: University of Cincinnati, College of Medicine
Kentaro Iwasawa: University of Cincinnati, College of Medicine
Kirsten Giesbrecht: University of Cincinnati, College of Medicine
Phillip C. Witcher: University of Cincinnati, College of Medicine
Alexandra Eicher: University of Cincinnati, College of Medicine
Lauren Haines: University of Cincinnati, College of Medicine
Yarim Lee: University of Cincinnati, College of Medicine
John M. Shannon: University of Cincinnati, College of Medicine
Mitsuru Morimoto: RIKEN Center for Biosystems Dynamics Research (BDR)
James M. Wells: University of Cincinnati, College of Medicine
Takanori Takebe: University of Cincinnati, College of Medicine
Aaron M. Zorn: University of Cincinnati, College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Visceral organs, such as the lungs, stomach and liver, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding splanchnic mesoderm (SM). While DE patterning is fairly well studied, the paracrine signaling controlling SM regionalization and how this is coordinated with epithelial identity is obscure. Here, we use single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This identifies a diversity of SM cell types that develop in close register with the organ-specific epithelium. We infer a spatiotemporal signaling network of endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validate key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging these signaling interactions, we generate different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell .

Date: 2020
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DOI: 10.1038/s41467-020-17968-x

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