The single-cell chromatin landscape in gonadal cell lineage specification

BMC Genomics. 2024 May 13;25(1):464. doi: 10.1186/s12864-024-10376-1.

Abstract

Gonad development includes sex determination and divergent maturation of the testes and ovaries. Recent advances in measuring gene expression in single cells are providing new insights into this complex process. However, the underlying epigenetic regulatory mechanisms remain unclear. Here, we profiled chromatin accessibility in mouse gonadal cells of both sexes from embryonic day 11.5 to 14.5 using single-cell assay for transposase accessible chromatin by sequencing (scATAC-seq). Our results showed that individual cell types can be inferred by the chromatin landscape, and that cells can be temporally ordered along developmental trajectories. Integrative analysis of transcriptomic and chromatin-accessibility maps identified multiple putative regulatory elements proximal to key gonadal genes Nr5a1, Sox9 and Wt1. We also uncover cell type-specific regulatory factors underlying cell type specification. Overall, our results provide a better understanding of the epigenetic landscape associated with the progressive restriction of cell fates in the gonad.

Keywords: Chromatin accessibility; Gonad development; Regulatory genomics; Sex determination; Single-cell biology; Single-cell sequencing; scATAC-seq.

MeSH terms

  • Animals
  • Cell Lineage* / genetics
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Gonads* / cytology
  • Gonads* / embryology
  • Gonads* / metabolism
  • Male
  • Mice
  • Ovary / cytology
  • Ovary / metabolism
  • SOX9 Transcription Factor* / genetics
  • SOX9 Transcription Factor* / metabolism
  • Single-Cell Analysis*
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism
  • Testis / cytology
  • Testis / metabolism
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism

Substances

  • Chromatin
  • SOX9 Transcription Factor
  • steroidogenic factor 1, mouse
  • Steroidogenic Factor 1
  • WT1 Proteins
  • Sox9 protein, mouse
  • WT1 protein, mouse