Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach |
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Institution: | 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 |
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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 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. |
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Keywords: | Human gonad scRNA-seq Turner syndrome Leydig-Sertoli cell–cell interaction Gonocyte-to-spermatogonium transition |
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