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Volume 30, No 12, Dec 2020
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 30 Issue 12, December 2020: 1109-1126 |
Comparative analysis of cell lineage differentiation during hepatogenesis in humans and mice at the single-cell transcriptome level
Xin Wang1,† , Li Yang1,† , Yan-Chun Wang2,† , Zi-Ran Xu1 , Ye Feng1 , Jing Zhang2 , Yi Wang2 , Cheng-Ran Xu1,*
1Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Department of Human Anatomy, Histology, and Embryology, and School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100871, ChinaDuring embryogenesis, the liver is the site of hepatogenesis and hematopoiesis and contains many cell lineages derived from the endoderm and mesoderm. However, the characteristics and developmental programs of many of these cell lineages remain unclear, especially in humans. Here, we performed single-cell RNA sequencing of whole human and mouse fetal livers throughout development. We identified four cell lineage families of endoderm-derived, erythroid, non-erythroid hematopoietic, and mesoderm-derived non-hematopoietic cells, and defined the developmental pathways of the major cell lineage families. In both humans and mice, we identified novel markers of hepatic lineages and an ID3+ subpopulation of hepatoblasts as well as verified that hepatoblast differentiation follows the “default-directed” model. Additionally, we found that human but not mouse fetal hepatocytes display heterogeneity associated with expression of metabolism-related genes. We described the developmental process of erythroid progenitor cells during human and mouse hematopoiesis. Moreover, despite the general conservation of cell differentiation programs between species, we observed different cell lineage compositions during hematopoiesis in the human and mouse fetal livers. Taken together, these results reveal the dynamic cell landscape of fetal liver development and illustrate the similarities and differences in liver development between species, providing an extensive resource for inducing various liver cell lineages in vitro.
https://doi.org/10.1038/s41422-020-0378-6
