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

Summary: 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 se...

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Main Authors: Isabelle Stévant, Yasmine Neirijnck, Christelle Borel, Jessica Escoffier, Lee B. Smith, Stylianos E. Antonarakis, Emmanouil T. Dermitzakis, Serge Nef
Format: Article
Language:English
Published: Elsevier 2018-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718300755
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spelling doaj-6f5d4b3086434e71a0af795210bf9f012020-11-25T03:34:14ZengElsevierCell Reports2211-12472018-02-012261589159910.1016/j.celrep.2018.01.043Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA SequencingIsabelle Stévant0Yasmine Neirijnck1Christelle Borel2Jessica Escoffier3Lee B. Smith4Stylianos E. Antonarakis5Emmanouil T. Dermitzakis6Serge Nef7Department 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, SwitzerlandDepartment of Genetic Medicine and Development, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Genetic Medicine and Development, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Genetic Medicine and Development, University of Geneva, 1211 Geneva, SwitzerlandMRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK; School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, AustraliaDepartment of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, SwitzerlandDepartment 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, SwitzerlandDepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124718300755single-cell RNA-seqsex determinationtestisSertoli cellfetal Leydig cellprogenitors
collection DOAJ
language English
format Article
sources DOAJ
author Isabelle Stévant
Yasmine Neirijnck
Christelle Borel
Jessica Escoffier
Lee B. Smith
Stylianos E. Antonarakis
Emmanouil T. Dermitzakis
Serge Nef
spellingShingle Isabelle Stévant
Yasmine Neirijnck
Christelle Borel
Jessica Escoffier
Lee B. Smith
Stylianos E. Antonarakis
Emmanouil T. Dermitzakis
Serge Nef
Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
Cell Reports
single-cell RNA-seq
sex determination
testis
Sertoli cell
fetal Leydig cell
progenitors
author_facet Isabelle Stévant
Yasmine Neirijnck
Christelle Borel
Jessica Escoffier
Lee B. Smith
Stylianos E. Antonarakis
Emmanouil T. Dermitzakis
Serge Nef
author_sort Isabelle Stévant
title Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
title_short Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
title_full Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
title_fullStr Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
title_full_unstemmed Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing
title_sort deciphering cell lineage specification during male sex determination with single-cell rna sequencing
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2018-02-01
description Summary: 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.
topic single-cell RNA-seq
sex determination
testis
Sertoli cell
fetal Leydig cell
progenitors
url http://www.sciencedirect.com/science/article/pii/S2211124718300755
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