Abstract
Leydig cells (LCs) are the major androgen-producing cells in the testis. They arise from steroidogenic progenitors (SPs), whose origins, maintenance, and differentiation dynamics remain largely unknown. Single-cell transcriptomics reveal that the mouse steroidogenic lineage is specified as early as embryonic day 12.5 (E12.5) and has a dual mesonephric and coelomic origin. SPs specifically express the Wnt5a gene and evolve rapidly. At E12.5 and E13.5, they give rise first to an intermediate population of pre-LCs, and finally to fetal LCs. At E16.5, SPs possess the characteristics of the dormant progenitors at the origin of adult LCs and are also transcriptionally closely related to peritubular myoid cells (PMCs). In agreement with our in silico analysis, in vivo lineage tracing indicates that Wnt5a-expressing cells are bona fide progenitors of PMCs as well as fetal and adult LCs, contributing to most of the LCs present in the fetal and adult testis.
| Original language | English |
|---|---|
| Article number | 110935 |
| Journal | Cell Reports |
| Volume | 39 |
| Issue number | 11 |
| DOIs | |
| State | Published - 14 Jun 2022 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2022 The Author(s)
Funding
This work was supported by grants from the Swiss National Science Foundation (grants 31003A_173070 and 310030_200316) and by the Département de l'Instruction Publique of the State of Geneva (to S.N.). We thank Antonella Rauseo, Juliette Cicchini-Bauquis, Françoise Kühne, and Violaine Regard for their help in animal handling, genotyping, and immunofluorescence experiments, Fabrizio Thorel and Olivier Fazio from the transgenesis platform for their help in the generation of the transgenic knockin line Wnt5a:Tet-On3G (Faculty of Medicine, University of Geneva), the animal facility team (Faculty of Medicine, University of Geneva), Jean-Pierre Aubry, Cécile Gameiro, and Grégory Schneiter of the flow cytometry platform, the genomic platform, and Nicolas Liaudet of the bioimaging platform (Faculty of Medicine, University of Geneva) for his substantial contribution with the counting analysis. We thank also the members of the Nef laboratory for helpful discussion and critical reading of the manuscript. Conceptualization, H.A. C.D. C.M. and S.N.; methodology, H.A. C.D. and B.C.; investigation, H.A. C.D. and C.M.; formal analysis and data curation, H.A. C.D. C.M. Y.N. P.S. I.S. and C.M.R.; writing – original draft, C.D. H.A. and S.N.; funding acquisition, S.N.; resources, S.N.; supervision, S.N. The authors declare no competing interests. This work was supported by grants from the Swiss National Science Foundation (grants 31003A_173070 and 310030_200316 ) and by the Département de l'Instruction Publique of the State of Geneva (to S.N.). We thank Antonella Rauseo, Juliette Cicchini-Bauquis, Françoise Kühne, and Violaine Regard for their help in animal handling, genotyping, and immunofluorescence experiments, Fabrizio Thorel and Olivier Fazio from the transgenesis platform for their help in the generation of the transgenic knockin line Wnt5a:Tet-On3G (Faculty of Medicine, University of Geneva), the animal facility team (Faculty of Medicine, University of Geneva), Jean-Pierre Aubry, Cécile Gameiro, and Grégory Schneiter of the flow cytometry platform, the genomic platform, and Nicolas Liaudet of the bioimaging platform (Faculty of Medicine, University of Geneva) for his substantial contribution with the counting analysis. We thank also the members of the Nef laboratory for helpful discussion and critical reading of the manuscript.
| Funders | Funder number |
|---|---|
| Département de l'Instruction Publique of the State of Geneva | |
| Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | 310030_200316, 31003A_173070 |
| Université de Genève |
Keywords
- CP: Developmental biology
- Leydig cells
- WNT5A
- in vivo lineage tracing
- peritubular myoid cells
- scRNA-seq
- single-cell RNA sequencing
- steroidogenic progenitors
- testis