Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing

Isabelle Stévant, Yasmine Neirijnck, Christelle Borel, Jessica Escoffier, Lee B. Smith, Stylianos E. Antonarakis, Emmanouil T. Dermitzakis, Serge Nef

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

The gonad is a unique biological system for studying cell-fate decisions. However, major questions remain regarding the identity of somatic progenitor cells and the transcriptional events driving cell differentiation. Using time-series single-cell RNA sequencing on XY mouse gonads during sex determination, we identified a single population of somatic progenitor cells prior to sex determination. A subset of these progenitors differentiates into Sertoli cells, a process characterized by a highly dynamic genetic program consisting of sequential waves of gene expression. Another subset of multipotent cells maintains their progenitor state but undergoes significant transcriptional changes restricting their competence toward a steroidogenic fate required for the differentiation of fetal Leydig cells. Our findings confirm the presence of a unique multipotent progenitor population in the gonadal primordium that gives rise to both supporting and interstitial lineages. These also provide the most granular analysis of the transcriptional events occurring during testicular cell-fate commitment. Using single-cell RNA sequencing of gonadal somatic cells during male sex determination, Stévant et al. identify a single Nr5a1-expressing progenitor cell population before sex determination that undergoes temporal fate specification with competence windows to differentiate first toward Sertoli cells or later to fetal Leydig cells.

Original languageEnglish
Pages (from-to)1589-1599
Number of pages11
JournalCell Reports
Volume22
Issue number6
DOIs
StatePublished - 6 Feb 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018

Funding

This work was supported by grants from the Swiss National Science Foundation (grants 31003A_173070 and 51PHI0-141994) and by the Département de l'Instruction Publique of the State of Geneva. We thank Luciana Romano and Deborah Penet for the sequencing; Pascale Garlonne Ribaux, Françoise Kuhne, and Béatrice Conne for technical assistance; Cécile Gameiro from the flow cytometry facility for the cell sorting; and Didier Chollet, Brice Petit, and Mylène Docquier from the iGE3 Genomics Platform for the single-cell capture. We thank also the members of the Nef and Dermitzakis laboratories for the helpful discussions and critical reading of the manuscript. This work was supported by grants from the Swiss National Science Foundation (grants 31003A_173070 and 51PHI0-141994 ) and by the Département de l’Instruction Publique of the State of Geneva . We thank Luciana Romano and Deborah Penet for the sequencing; Pascale Garlonne Ribaux, Françoise Kuhne, and Béatrice Conne for technical assistance; Cécile Gameiro from the flow cytometry facility for the cell sorting; and Didier Chollet, Brice Petit, and Mylène Docquier from the iGE3 Genomics Platform for the single-cell capture. We thank also the members of the Nef and Dermitzakis laboratories for the helpful discussions and critical reading of the manuscript.

FundersFunder number
Département de l’Instruction Publique of the State of Geneva
Swiss National Science Foundation
Medical Research CouncilMR/N002970/1
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung31003A_173070, 51PHI0-141994

    Keywords

    • Sertoli cell
    • cell-fate decision
    • differentiation
    • fetal Leydig cell
    • gene expression
    • lineage specification
    • progenitors
    • sex determination
    • single-cell RNA-seq
    • testis

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