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

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

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.

Keywords: Sertoli cells; cell fate decision; differentiation; gene expression; gonad development; granulosa cell; lineage specification; ovary; progenitors; sex determination; single-cell RNA-seq; supporting cells; testis; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / physiology*
  • Female
  • Gene Expression Profiling*
  • Granulosa Cells / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Sertoli Cells / cytology
  • Sertoli Cells / metabolism*
  • Sex Determination Processes / physiology*
  • Single-Cell Analysis*