Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach  

作　　者：Rui Wang Xixi Liu Li Li Ming Yang Jun Yong Fan Zhai Lu Wen Liying Yan Jie Qiao Fuchou Tang 

机构地区：[1]Biomedical Pioneering Innovation Center,Department of Obstetrics and Gynecology,Third Hospital,School of Life Sciences,Peking University,Beijing 100871,China [2]Beijing Advanced Innovation Center for Genomics and Center for Reproductive Medicine,Third Hospital,Peking University,Beijing 100191,China [3]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China [4]Key Laboratory of Assisted Reproduction and Key Laboratory of Cell Proliferation and Differentiation,Ministry of Education,Beijing 100191,China [5]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology,Beijing 100191,China [6]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China

出　　处：《Genomics, Proteomics & Bioinformatics》2022年第2期223-245,共23页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Key R&D Program of China(Grant No.2018YFA0107601).

摘　　要：Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development.Here,using a time-series single-cell RNA sequencing(scRNA-seq)strategy,we analyzed fetal germ cells(FGCs)and gonadal somatic cells in human embryos and fetuses.Clustering analysis of testes and ovaries revealed several novel cell subsets,including POU5F1^(+)SPARC^(+)FGCs and KRT19^(+) somatic cells.Furthermore,our data indicated that the bone morphogenetic protein(BMP)signaling pathway plays cell type-specific and developmental stage-specific roles in testis development and promotes the gonocyte-to-spermatogonium transition(GST)in late-stage testicular mitotic arrest FGCs.Intriguingly,testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a stepwise manner.In our study,potential interactions between gonadal somatic cells were systematically explored and we identified cell type-specific developmental defects in both FGCs and gonadal somatic cells in a Turner syndrome embryo(45,XO).Our work provides a blueprint of the complex yet highly ordered development of and the interactions among human FGCs and gonadal somatic cells.

关 键 词：Human gonad scRNA-seq Turner syndrome Leydig-Sertoli cell-cell interaction Gonocyte-tospermatogonium transition 

分 类 号：R394[医药卫生—医学遗传学]