The single-cell chromatin accessibility landscape in mouse perinatal testis development
- Chinese University of Hong Kong, Hong Kong
- Fujian Medical University, China
- Guangzhou Institutes of Biomedicine and Health, China
- Hudson Institute of Medical Research, Australia
Abstract
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.
Data availability
All raw and processed sequencing data generated in this study have been submitted to the NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE164439. Code for producing the majority of analyses from this paper is available on GitHub at https://github.com/liaojinyue/mouse_testis_scATAC.
-
Genome-wide maps of chromatin state in mouse perinatal testes [scATAC-seq]NCBI Gene Expression Omnibus, GSE164439.
-
Single-cell RNAseq analysis of testicular germ and somatic cell development during the perinatal periodNCBI Gene Expression Omnibus, GSE130593.
Article and author information
Author details
Funding
Chinese University of Hong Kong (Department of Chemical Pathology's Faculty Startup Fund)
- Jinyue Liao
University Grants Committee (General Research Fund CUHK 14120418)
- Tin-lap Lee
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the animal experiments were performed according to the protocols approved by the Animal Experiment Ethics Committee (AEEC) of The Chinese University of Hong Kong (CUHK) and followed the Animals (Control of Experiments) Ordinance (Cap. 340) licensed from the Department of Health, the Government of Hong Kong Special Administrative Region.
Copyright
© 2023, Suen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,106
- views
-
- 297
- downloads
-
- 4
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Further reading
-
- Chromosomes and Gene Expression
RNA interference (RNAi) is a conserved pathway that utilizes Argonaute proteins and their associated small RNAs to exert gene regulatory function on complementary transcripts. While the majority of germline-expressed RNAi proteins reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here, we find that the small RNA biogenesis machinery is spatially and temporally organized during Caenorhabditis elegans embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we further demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.
-
- Chromosomes and Gene Expression
- Genetics and Genomics
A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.
