关键词: Chromatin accessibility Gonad development Regulatory genomics Sex determination Single-cell biology Single-cell sequencing scATAC-seq

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

来  源:   DOI:10.1186/s12864-024-10376-1   PDF(Pubmed)

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.
摘要:
性腺发育包括睾丸和卵巢的性别决定和不同的成熟。测量单细胞中基因表达的最新进展为这一复杂过程提供了新的见解。然而,潜在的表观遗传调控机制仍不清楚.这里,我们通过测序(scATAC-seq),使用转座酶可接近染色质的单细胞测定法,对胚胎11.5天至14.5天的小鼠性腺细胞中染色质的可接近性进行了分析。我们的结果表明,单个细胞类型可以通过染色质景观推断,细胞可以沿着发育轨迹在时间上排序。转录组和染色质可及性图的综合分析确定了邻近关键性腺基因Nr5a1,Sox9和Wt1的多个推定调节元件。我们还揭示了细胞类型特异性调节因子的细胞类型规格。总的来说,我们的研究结果为更好地理解与性腺中细胞命运的进行性限制相关的表观遗传景观提供了更好的理解.
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