Comparative analysis of cell lineage differentiation during hepatogenesis in humans and mice at the single-cell transcriptome level  

作　　者：Xin Wang Li Yang Yan-Chun Wang Zi-Ran Xu Ye Feng Jing Zhang Yi Wang Cheng-Ran Xu 

机构地区：[1]Ministry 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,China [2]Haidian Maternal&Child Health Hospital,Beijing 100080,China

出　　处：《Cell Research》2020年第12期1109-1126,共18页细胞研究（英文版）

基　　金：the National Key R&D Program of China(2019YFA0801500);the National Basic Research Program of China(2015CB942800);the National Natural Science Foundation of China(31521004,31522036);the SLS-Qidong Innovation Fund,as well as funding from the Peking-Tsinghua Center for Life Sciences to C.-R.X.

摘　　要：During 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.

关 键 词：hepato FETAL METABOLISM 

分 类 号：Q2[生物学—细胞生物学]