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Learn MoreSpermatogonial stem cells (SSCs) are critical for maintaining spermatogenesis throughout adult life. Little is known about how SSCs are first generated. Here, we report the identification of a transcription factorRHOX10that promotes the initial establishment of SSCs. We were led to this discovery because we found that conditional loss of a large X-linked gene cluster comprised of 33 related homeobox genes, including Rhox10, causes defects predicted if SSCs fail to be generated or maintained. Remarkably, KO of only Rhox10 elicits SSC-related defects indistinguishable from KO of the entire gene cluster. Using a battery of approaches, including single cell-RNAseq analysis, we determined that loss of Rhox10 causes accumulation of undifferentiated germ cellsPro-spermatogonia (ProSG)at a time when they normally would form SSCs. The identification of a transcription factor that drives the initial generation of SSCs has potential therapeutic applications for infertility. SOURCE: Kun Zhang UCSD
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