SOX3 promotes generation of committed spermatogonia in postnatal mouse testes

Abstract

SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. Sox3 is also expressed in other locations, notably within the spermatogonial stem/progenitor cell population in postnatal testis. Independent studies have shown that Sox3 null mice exhibit a spermatogenic block as young adults, the mechanism of which remains poorly understood. Using a panel of spermatogonial cell marker genes, we demonstrate that Sox3 is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool. Additionally, we use a Sox3 null mouse model to define a potential role for this factor in progenitor cell function. We demonstrate that Sox3 expression is required for transition of undifferentiated cells from a GFRα1+ self-renewing state to the NGN3 + transit-amplifying compartment. Critically, using chromatin immunoprecipitation, we demonstrate that SOX3 binds to a highly conserved region in the Ngn3 promoter region in vivo, indicating that Ngn3 is a direct target of SOX3. Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells.

Nutrient restriction synergizes with retinoic acid to induce mammalian meiotic initiation in vitro

“…Recently, Sohlh1 is shown to regulate meiotic gene expression ( Sycp1 , Sycp3 ) by directly binding to their proximal promoters 45 . Sox3 is expressed exclusively in spermatogonia committed to differentiation 46 , and loss of Sox3 impairs early meiosis, including a downregulation of Sycp3 expression in young adult testes 47 . Thus, these data suggest that nutrient restriction induces a distinct network of TFs to complement RA signaling in the meiotic gene activation (Fig.…”

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors

“…While these genes comprised only 0.4% of expressed protein-coding genes in undifferentiated spermatogonia (53 of 13,497 expressed genes), they represented 1.1% of DAZL targets (29 genes of 2,633 DAZL targets), representing an enrichment of spermatogonial factors ( Figure 2D ; one-tailed hypergeometric test; p=1.71×10 −8 ). Two of these DAZL-targeted factors, Lin28a and Sox3 , promote the formation and proliferation of progenitor spermatogonia ( Chakraborty et al, 2014 ; McAninch et al, 2020 ) and may contribute to the diminished progenitor population observed in the Dazl cKO ( Figure 2E ). Additional factors, such as Foxo1 , Kit , Rarg , and Sall4 , promote spermatogonial differentiation ( de Rooij et al, 1999 ; Gely-Pernot et al, 2012 ; Goertz et al, 2011 ; Hobbs et al, 2012 ; Yoshinaga et al, 1991 ), consistent with the reduced spermatogonial differentiation in the Dazl cKO ( Figure 2E ).…”

Distinctive molecular features of regenerative stem cells in the damaged male germline

“…Progenitors exhibited activity of RARγ, SOX3 and SALL1. SOX3 and RARγ play key roles in SSC differentiation priming, validating cluster identity 38 , 39 . Proliferative SSC clusters were regulated by similar transcription factors including EGR3, HES1, HIF1A and DMRT3 while transitional A undiff were distinguished by activity of E2F7, E2F2 and EZH2 regulons.…”