CITED2 Binding to EP300 Regulates Human Spermatogonial Stem Cell Proliferation and Survival Through HSPA6

TL;DR

This study shows how CITED2 and EP300 regulate human spermatogonial stem cell growth and survival through HSPA6, offering new insights into male fertility mechanisms.

Contribution

The novel contribution is identifying CITED2's role in regulating human SSC proliferation and survival via HSPA6, which was previously unknown.

Findings

CITED2 is dominantly expressed in human spermatogonial stem cells.

CITED2 interacts with EP300 and influences the MAPK pathway and HSPA6 gene expression.

HSPA6 overexpression counteracts the effects of CITED2 knockdown on cell proliferation and apoptosis.

Abstract

Spermatogonial stem cells (SSCs) are essential for the initiation and continuation of spermatogenesis, a process fundamental to male fertility. Despite extensive studies on mouse SSCs, the mechanisms governing self-renewal and differentiation in human SSCs remain to be elucidated. This study investigated the regulatory mechanisms of SSCs by analyzing single-cell sequencing data from the GEO dataset of human testis. Analysis revealed dominant expression of CITED2 in human SSCs. Reduction of CITED2 levels in hSSC lines significantly inhibited proliferation and increased apoptosis. Protein interaction prediction and immunoprecipitation identified interactions between CITED2 and EP300 in SSC lines. RNA sequencing results indicated that CITED2 knockdown significantly affected the MAPK pathway and the HSPA6 gene. Overexpression of HSPA6 mitigated the proliferative and apoptotic changes provoked by CITED2 downregulation. These findings provide novel insights into the regulatory and functional mechanisms of CITED2-mediated hSSC development.

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