RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade
Copyright policy )RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade
Spermatogonial stem cells (SSCs) are essential for male fertility. Here, we report that mouse SSC generation is driven by a transcription factor (TF) cascade controlled by the homeobox protein, RHOX10, which acts by driving the differentiation of SSC precursors called pro-spermatogonia (ProSG). We identify genes regulated by RHOX10 in ProSG in vivo and define direct RHOX10-target genes using several approaches, including a rapid temporal induction assay: iSLAMseq. Together, these approaches identify temporal waves of RHOX10 direct targets, as well as RHOX10 secondary-target genes. Many of the RHOX10-regulated genes encode proteins with known roles in SSCs. Using an in vitro ProSG differentiation assay, we find that RHOX10 promotes mouse ProSG differentiation through a conserved transcriptional cascade involving the key germ-cell TFs DMRT1 and ZBTB16. Our study gives important insights into germ cell development and provides a blueprint for how to define TF cascades.
- University of California, San Diego United States
- University of California System United States
- UNIVERSITY OF CALIFORNIA, SAN DIEGO
- University of California, San Diego United States
- University of California, San Francisco United States
Male, Transcription, Genetic, Medical Physiology, Spermatogonial stem cells, Inbred C57BL, DMRT1, Mice, homeobox gene, 2.1 Biological and endogenous factors, Developmental, Promyelocytic Leukemia Zinc Finger Protein, Aetiology, transcription factor, single-cell RNA-seq, Genome, Stem Cells, homeobox, RHOX10, Gene Expression Regulation, Developmental, Cell Differentiation, SLAM-seq, Biological Sciences, ZBTB16, Biological sciences, Stem Cell Research - Nonembryonic - Non-Human, prospermatogonia, Transcription, Biotechnology, Signal Transduction, Transcriptional Activation, 570, gonocyte, 1.1 Normal biological development and functioning, 610, Article, Rare Diseases, Genetic, Underpinning research, Genetics, Animals, Humans, spermatogonial stem cells, Homeodomain Proteins, Base Sequence, Contraception/Reproduction, Inflammatory and immune system, Stem Cell Research, Spermatogonia, Mice, Inbred C57BL, Germ Cells, HEK293 Cells, Gene Expression Regulation, pro-spermatogonia, Biochemistry and Cell Biology, Generic health relevance, Transcription Factors
Male, Transcription, Genetic, Medical Physiology, Spermatogonial stem cells, Inbred C57BL, DMRT1, Mice, homeobox gene, 2.1 Biological and endogenous factors, Developmental, Promyelocytic Leukemia Zinc Finger Protein, Aetiology, transcription factor, single-cell RNA-seq, Genome, Stem Cells, homeobox, RHOX10, Gene Expression Regulation, Developmental, Cell Differentiation, SLAM-seq, Biological Sciences, ZBTB16, Biological sciences, Stem Cell Research - Nonembryonic - Non-Human, prospermatogonia, Transcription, Biotechnology, Signal Transduction, Transcriptional Activation, 570, gonocyte, 1.1 Normal biological development and functioning, 610, Article, Rare Diseases, Genetic, Underpinning research, Genetics, Animals, Humans, spermatogonial stem cells, Homeodomain Proteins, Base Sequence, Contraception/Reproduction, Inflammatory and immune system, Stem Cell Research, Spermatogonia, Mice, Inbred C57BL, Germ Cells, HEK293 Cells, Gene Expression Regulation, pro-spermatogonia, Biochemistry and Cell Biology, Generic health relevance, Transcription Factors
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