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Cell Rep. 2019 Mar 19;26(12):3272-3283.e3. doi: 10.1016/j.celrep.2019.02.069.

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

Author information

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; SIB, Swiss Institute of Bioinformatics, University of Geneva, 1211 Geneva, Switzerland.
2
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
3
Mammalian Genetics Unit, Medical Research Council, Harwell Institute, Oxfordshire OX11 0RD, UK.
4
Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
5
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.

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.

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

PMID:
30893600
DOI:
10.1016/j.celrep.2019.02.069
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