Volume 31, No 3, Mar 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 3, March 2021: 326-344

ORIGINAL ARTICLES

Single-cell patterning and axis characterization in the murine and human definitive endoderm

Lin-Chen Li^1,2,3 , Xin Wang¹ , Zi-Ran Xu^1,4 , Yan-Chun Wang⁵ , Ye Feng^1,4 , Liu Yang^1,2 , Wei-Lin Qiu^1,4 , Li Yang^1,2 , Xin-Xin Yu¹ , Jun Gu³ , Cheng-Ran Xu^1,*

¹Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences; Department of Human Anatomy, Histology, and Embryology, School of Basic Medical Sciences; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
²Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
³Beijing Institute of Collaborative Innovation, Beijing 100094, China
⁴PKU-Tsinghua-NIBS Graduate Program, Peking University, Beijing 100871, China
⁵Haidian Maternal & Child Health Hospital, Beijing 100080, China
These authors contributed equally: Lin-Chen Li, Xin Wang, Zi-Ran Xu, Yan-Chun Wang Correspondence: Cheng-Ran Xu(cxu@pku.edu.cn)

Defining the precise regionalization of specified definitive endoderm progenitors is critical for understanding the mechanisms underlying the generation and regeneration of respiratory and digestive organs, yet the patterning of endoderm progenitors remains unresolved, particularly in humans. We performed single-cell RNA sequencing on endoderm cells during the early somitogenesis stages in mice and humans. We developed molecular criteria to define four major endoderm regions (foregut, lip of anterior intestinal portal, midgut, and hindgut) and their developmental pathways. We identified the cell subpopulations in each region and their spatial distributions and characterized key molecular features along the body axes. Dorsal and ventral pancreatic progenitors appear to originate from the midgut population and follow distinct pathways to develop into an identical cell type. Finally, we described the generally conserved endoderm patterning in humans and clear differences in dorsal cell distribution between species. Our study comprehensively defines single-cell endoderm patterning and provides novel insights into the spatiotemporal process that drives establishment of early endoderm domains.

https://doi.org/10.1038/s41422-020-00426-0

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