Dissecting Cell Lineage Specification and Sex Fate Determination in Gonadal Somatic Cells Using Single-Cell Transcriptomics

Isabelle Stévant, Françoise Kühne, Andy Greenfield, Marie Christine Chaboissier, Emmanouil T. Dermitzakis, Serge Nef

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP + somatic cells during sex determination, we identified a single population of early progenitors giving rise to both pre-granulosa cells and potential steroidogenic precursor cells. By comparing time series single-cell RNA sequencing of XX and XY somatic cells, we provide evidence that gonadal supporting cells are specified from these early progenitors by a non-sex-specific transcriptomic program before pre-granulosa and Sertoli cells acquire their sex-specific identity. In XX and XY steroidogenic precursors, similar transcriptomic profiles underlie the acquisition of cell fate but with XX cells exhibiting a relative delay. Our data provide an important resource, at single-cell resolution, for further interrogation of the molecular and cellular basis of mammalian sex determination.

Original languageEnglish
Pages (from-to)3272-3283.e3
JournalCell Reports
Volume26
Issue number12
DOIs
StatePublished - 19 Mar 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Author(s)

Funding

This work was supported by grants from the Swiss National Science Foundation ( 31003A_173070 and 51PHI0-141994 ) and by the Département de l’Instruction Publique of the State of Geneva (to S.N.). We thank Luciana Romano and Deborah Penet for the sequencing. We thank also the members of the Nef and Dermitzakis laboratories for helpful discussion and critical reading of the manuscript, 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. This work was supported by grants from the Swiss National Science Foundation (31003A_173070 and 51PHI0-141994) and by the D?partement de l'Instruction Publique of the State of Geneva (to S.N.). We thank Luciana Romano and Deborah Penet for the sequencing. We thank also the members of the Nef and Dermitzakis laboratories for helpful discussion and critical reading of the manuscript, C?cile Gameiro from the flow cytometry facility for the cell sorting, and Didier Chollet, Brice Petit, and Myl?ne Docquier from the iGE3 Genomics Platform for the single-cell capture.

FundersFunder number
D?partement de l'Instruction Publique of the State of Geneva
Département de l’Instruction Publique of the State of Geneva
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung31003A_173070, 51PHI0-141994

    Keywords

    • Sertoli cells
    • cell fate decision
    • differentiation
    • gene expression
    • gonad development
    • granulosa cell
    • lineage specification
    • ovary
    • progenitors
    • sex determination
    • single-cell RNA-seq
    • supporting cells
    • testis
    • transcriptomics

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