Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland; SIB, Swiss Institute of Bioinformatics, University of Geneva, 1211 Geneva, Switzerland.
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
Cell Rep. 2018 Feb 6;22(6):1589-1599. doi: 10.1016/j.celrep.2018.01.043.
The gonad is a unique biological system for studying cell-fate decisions. However, major questions remain regarding the identity of somatic progenitor cells and the transcriptional events driving cell differentiation. Using time-series single-cell RNA sequencing on XY mouse gonads during sex determination, we identified a single population of somatic progenitor cells prior to sex determination. A subset of these progenitors differentiates into Sertoli cells, a process characterized by a highly dynamic genetic program consisting of sequential waves of gene expression. Another subset of multipotent cells maintains their progenitor state but undergoes significant transcriptional changes restricting their competence toward a steroidogenic fate required for the differentiation of fetal Leydig cells. Our findings confirm the presence of a unique multipotent progenitor population in the gonadal primordium that gives rise to both supporting and interstitial lineages. These also provide the most granular analysis of the transcriptional events occurring during testicular cell-fate commitment.
性腺是研究细胞命运决定的独特生物系统。然而,关于体祖细胞的身份和驱动细胞分化的转录事件,仍存在一些重要问题。我们对性决定过程中 XY 鼠性腺的时间序列单细胞 RNA 测序进行了研究,在性决定之前确定了一个单一的体祖细胞群体。这些祖细胞的一部分分化为支持细胞,这一过程的特征是一个高度动态的遗传程序,由基因表达的连续波组成。另一部分多能细胞保持其祖细胞状态,但经历了显著的转录变化,限制了它们向胎儿睾丸间质细胞分化所需的类固醇生成命运的能力。我们的研究结果证实了在性腺原基中存在一种独特的多能祖细胞群体,它可以产生支持细胞和间质细胞谱系。这些研究还提供了对睾丸细胞命运决定过程中发生的转录事件的最详细分析。