Abstract
AbstractVisceral 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference55 articles.
1. Kraus, M. R. & Grapin-Botton, A. Patterning and shaping the endoderm in vivo and in culture. Curr. Opin. Genet. Dev. 22, 347–353 (2012).
2. Zorn, A. M. & Wells, J. M. Vertebrate endoderm development and organ formation. Annu Rev. Cell Dev. Biol. 25, 221–251 (2009).
3. Le Douarin, N. & Houssaint, E. Role of the mesoderm in the induction of the synthesis of glycogen during differentiation of the hepatic endoderm. C. R. Acad. Hebd. Seances Acad. Sci. D. 264, 1872–1874 (1967).
4. Ferretti, E. & Hadjantonakis, A. K. Mesoderm specification and diversification: from single cells to emergent tissues. Curr. Opin. Cell Biol. 61, 110–116 (2019).
5. Sweetman, D., Wagstaff, L., Cooper, O., Weijer, C. & Munsterberg, A. The migration of paraxial and lateral plate mesoderm cells emerging from the late primitive streak is controlled by different Wnt signals. BMC Dev. Biol. 8, 63 (2008).
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