Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach
- Author:
Wang RUI
1
;
Liu XIXI
;
Li LI
;
Yang MING
;
Yong JUN
;
Zhai FAN
;
Wen LU
;
Yan LIYING
;
Qiao JIE
;
Tang FUCHOU
Author Information
1. Biomedical Pioneering Innovation Center,Department of Obstetrics and Gynecology,Third Hospital,School of Life Sciences,Peking University,Beijing 100871,China;Beijing Advanced Innovation Center for Genomics and Center for Reproductive Medicine,Third Hospital,Peking University,Beijing 100191,China;Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China;Key Laboratory of
- Keywords:
Human gonad;
scRNA-seq;
Turner syndrome;
Leydig-Sertoli cell-cell interaction;
Gonocyte-to-spermatogonium transition
- From:
Genomics, Proteomics & Bioinformatics
2022;20(2):223-245
- CountryChina
- Language:Chinese
-
Abstract:
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 develop-mental 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 devel-opment of and the interactions among human FGCs and gonadal somatic cells.
