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Single-cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

Chassot, Anne-Amandine
Chaboissier, Marie-Christine
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Published in The FASEB journal. 2021, vol. 35, no. 4, e21452
Abstract Despite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14 914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the bone morphogenic protein (BMP) and nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data are available on a web platform and provide a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function, and disease.
PMID: 33749946
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Article (Published version) (3.3 MB) - public document Free access
Research group Mécanismes moléculaires et génétiques du développement sexuel (778)
Swiss National Science Foundation: 31003A_173070
(ISO format)
MAYERE, Chloé et al. Single-cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination. In: FASEB Journal, 2021, vol. 35, n° 4, p. e21452. doi: 10.1096/fj.202002420R https://archive-ouverte.unige.ch/unige:154101

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Deposited on : 2021-08-24

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