The single-cell chromatin accessibility landscape in mouse perinatal testis development.
Hoi Ching SuenShitao RaoAlfred Chun Shui LukRuoyu ZhangLele YangHuayu QiHon Cheong SoRobin M HobbsTin-Lap LeeJinyue LiaoPublished in: eLife (2023)
Spermatogenesis depends on an orchestrated series of developing events in germ cells and full maturation of the somatic microenvironment. To date, the majority of efforts to study cellular heterogeneity in testis has been focused on single-cell gene expression rather than the chromatin landscape shaping gene expression. To advance our understanding of the regulatory programs underlying testicular cell types, we analyzed single-cell chromatin accessibility profiles in more than 25,000 cells from mouse developing testis. We showed that scATAC-Seq allowed us to deconvolve distinct cell populations and identify cis-regulatory elements (CREs) underlying cell type specification. We identified sets of transcription factors associated with cell type-specific accessibility, revealing novel regulators of cell fate specification and maintenance. Pseudotime reconstruction revealed detailed regulatory dynamics coordinating the sequential developmental progressions of germ cells and somatic cells. This high-resolution dataset also unveiled previously unreported subpopulations within both the Sertoli and Leydig cell groups. Further, we defined candidate target cell types and genes of several GWAS signals, including those associated with testosterone levels and coronary artery disease. Collectively, our data provide a blueprint of the 'regulon' of the mouse male germline and supporting somatic cells.
Keyphrases
- single cell
- rna seq
- gene expression
- induced apoptosis
- transcription factor
- cell cycle arrest
- high throughput
- coronary artery disease
- high resolution
- cell fate
- genome wide
- dna methylation
- stem cells
- machine learning
- oxidative stress
- dna damage
- pregnant women
- copy number
- mesenchymal stem cells
- acute coronary syndrome
- pi k akt
- cardiovascular disease
- germ cell
- big data
- aortic valve
- public health
- artificial intelligence
- cell proliferation
- quality improvement
- cardiovascular events
- smoking cessation
- genome wide identification