Dissecting Cell Lineage Specification and Sex Fate Determination in Gonadal Somatic Cells Using Single-Cell Transcriptomics.
Cell Rep. 2019 Mar 19;26(12):3272-3283.e3. doi: 10.1016/j.celrep.2019.02.069.
Stévant I1, Kühne F2, Greenfield A3, Chaboissier MC4, Dermitzakis ET1, Nef S5.
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.
PMID: 30893600
DOI:10.1016/j.celrep.2019.02.069