The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

Autor: Adrienne H. Zhao, Eric Babajanian, Eleen Shum, Vaishnavi Sridhar, Marcy E. Richardson, Terra-Dawn M. Plank, Hye-Won Song, Meena Sukhwani, Dirk G. de Rooij, Anilkumar Bettegowda, David Skarbrevik, Blue B. Lake, Mimi H. Phan, Kyle E. Orwig, Kun Zhang, Madhuvanthi Ramaiah, Miles F. Wilkinson
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Medical Physiology
Regenerative Medicine
Mice
0302 clinical medicine
Single-cell analysis
Genes
X-Linked

2.1 Biological and endogenous factors
Protein Isoforms
Developmental
Aetiology
gonocytes
skin and connective tissue diseases
lcsh:QH301-705.5
transcription factor
Genetics
Mice
Knockout

030219 obstetrics & reproductive medicine
integumentary system
Adult Germline Stem Cells
homeobox
Gene Expression Regulation
Developmental

Phenotype
Rhox
medicine.anatomical_structure
Multigene Family
Stem Cell Research - Nonembryonic - Non-Human
prospermatogonia
Stem cell
Single-Cell Analysis
Sequence Analysis
Germ cell
Adult stem cell
endocrine system
Knockout
1.1 Normal biological development and functioning
Biology
General Biochemistry
Genetics and Molecular Biology

03 medical and health sciences
Rare Diseases
Underpinning research
medicine
Animals
Genes
Developmental

Spermatogenesis
Transcription factor
spermatogonial stem cells
Homeodomain Proteins
Sequence Analysis
RNA

germ line stem cell
germ cell
X-Linked
Stem Cell Research
Spermatogonia
030104 developmental biology
Gene Expression Regulation
Genes
lcsh:Biology (General)
RNA
Homeobox
Generic health relevance
Biochemistry and Cell Biology
Zdroj: Cell Reports, Vol 17, Iss 1, Pp 149-164 (2016)
Cell reports, vol 17, iss 1
ISSN: 2211-1247
Popis: SummaryThe developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor—RHOX10—critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.
Databáze: OpenAIRE