Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach
- Author:
Wang RUI
1
,
2
,
3
,
4
;
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
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
- 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.
