Deciphering the origins and fates of steroidogenic lineages in the mouse testis

Herta Ademi; Cyril Djari; Chloé Mayère; Yasmine Neirijnck; Pauline Sararols; Chris M Rands; Isabelle Stévant; Béatrice Conne; Serge Nef

doi:10.1016/j.celrep.2022.110935

Deciphering the origins and fates of steroidogenic lineages in the mouse testis

Cell Rep. 2022 Jun 14;39(11):110935. doi: 10.1016/j.celrep.2022.110935.

Authors

Herta Ademi¹, Cyril Djari¹, Chloé Mayère¹, Yasmine Neirijnck¹, Pauline Sararols¹, Chris M Rands², Isabelle Stévant¹, Béatrice Conne³, Serge Nef⁴

Affiliations

¹ Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland.
² Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
³ Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
⁴ Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland. Electronic address: serge.nef@unige.ch.

PMID: 35705036
DOI: 10.1016/j.celrep.2022.110935

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.

Keywords: CP: Developmental biology; Leydig cells; WNT5A; in vivo lineage tracing; peritubular myoid cells; scRNA-seq; single-cell RNA sequencing; steroidogenic progenitors; testis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androgens
Animals
Cell Differentiation
Fetus
Leydig Cells*
Male
Mice
Testis*

Substances

Androgens