Givelet M, Firlej V, Lassalle B, Gille AS, Lapoujade C, Holtzman I, Jarysta A, Haghighirad F, Dumont F, Jacques S, Letourneur F, Pflumio F, Allemand I, Patrat C, Thiounn N, Wolf JP, Riou L, Barraud-Lange V, and Fouchet P
Male infertility is responsible for approximately half of all cases of reproductive issues. Spermatogenesis originates in a small pool of spermatogonial stem cells (SSCs), which are of interest for therapy of infertility but remain not well defined in humans. Using multiparametric analysis of the side population (SP) phenotype and the α-6 integrin, THY1, and β-2 microglobulin cell markers, we identified a population of human primitive undifferentiated spermatogonia with the phenotype β-2 microglobulin (β-2M) - SPα-6 + THY1 + , which is highly enriched in stem cells. By analyzing the expression signatures of this SSC-enriched population along with other germinal progenitors, we established an exhaustive transcriptome of human spermatogenesis. Transcriptome profiling of the human β-2M - SPα-6 + THY1 + population and comparison with the profile of mouse undifferentiated spermatogonia provide insights into the molecular networks and key transcriptional regulators regulating human SSCs, including the basic-helix-loop-helix (bHLH) transcriptional repressor HES1, which we show to be implicated in maintenance of SSCs in vitro., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)