利用单细胞转录组学解析性腺体细胞中的细胞谱系特化和性别决定。

Dissecting Cell Lineage Specification and Sex Fate Determination in Gonadal Somatic Cells Using Single-Cell Transcriptomics.

机构信息

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.

出版信息

Cell Rep. 2019 Mar 19;26(12):3272-3283.e3. doi: 10.1016/j.celrep.2019.02.069.

DOI:10.1016/j.celrep.2019.02.069

PMID:30893600

Abstract

Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP somatic cells during sex determination, we identified a single population of early progenitors giving rise to both pre-granulosa cells and potential steroidogenic precursor cells. By comparing time series single-cell RNA sequencing of XX and XY somatic cells, we provide evidence that gonadal supporting cells are specified from these early progenitors by a non-sex-specific transcriptomic program before pre-granulosa and Sertoli cells acquire their sex-specific identity. In XX and XY steroidogenic precursors, similar transcriptomic profiles underlie the acquisition of cell fate but with XX cells exhibiting a relative delay. Our data provide an important resource, at single-cell resolution, for further interrogation of the molecular and cellular basis of mammalian sex determination.

摘要

性别决定是一个独特的过程，它允许研究多能祖细胞及其在性腺分化为睾丸或卵巢过程中获得性别特异性命运。我们使用时间序列单细胞 RNA 测序 (scRNA-seq) 对性别决定过程中的卵巢 Nr5a1-GFP 体细胞进行研究，鉴定出一个早期祖细胞群体，这些细胞可以产生原始卵泡细胞和潜在的类固醇生成前体细胞。通过比较 XX 和 XY 体细胞的时间序列单细胞 RNA 测序，我们提供的证据表明，性腺支持细胞是由这些早期祖细胞通过非性别特异性转录组程序特化而来的，然后原始卵泡细胞和支持细胞获得其性别特异性身份。在 XX 和 XY 类固醇生成前体细胞中，相似的转录组图谱是细胞命运获得的基础，但 XX 细胞表现出相对延迟。我们的数据提供了一个重要的资源，以单细胞分辨率，进一步探究哺乳动物性别决定的分子和细胞基础。