关键词： DMRT1 RHOX10 SLAM-seq ZBTB16 gonocyte homeobox pro-spermatogonia single-cell RNA-seq spermatogonial stem cells transcription factor

Mesh ： Animals Base Sequence Cell Differentiation / genetics Gene Expression Regulation, Developmental Genome Germ Cells / metabolism HEK293 Cells Homeodomain Proteins / metabolism Humans Male Mice, Inbred C57BL Promyelocytic Leukemia Zinc Finger Protein / metabolism Signal Transduction Spermatogonia / cytology Stem Cells / cytology metabolism Transcription Factors / metabolism Transcription, Genetic Transcriptional Activation / genetics Mice

来  源：   DOI：10.1016/j.celrep.2021.109423   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
摘要：
精原干细胞(SSC)是男性生育力所必需的。这里,我们报告说，小鼠SSC的产生是由同源异型盒蛋白控制的转录因子（TF）级联驱动的，RHOX10，通过驱动称为前精原细胞（ProSG）的SSC前体的分化而起作用。我们鉴定了体内ProSG中RHOX10调控的基因，并使用几种方法定义了直接的RHOX10靶基因，包括快速时间诱导测定：iSLAMseq。一起,这些方法识别RHOX10直接目标的时间波，以及RHOX10二级靶基因。许多RHOX10调节的基因编码在SSC中具有已知作用的蛋白质。使用体外ProSG分化试验，我们发现RHOX10通过涉及关键生殖细胞TFsDMRT1和ZBTB16的保守转录级联来促进小鼠ProSG分化。我们的研究为生殖细胞发育提供了重要的见解，并为如何定义TF级联提供了蓝图。
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