Transcriptomic profiling reveals the extensive involvement of HtrA4 during trophoblast stem cell differentiation into syncytiotrophoblast

ABSTRACT: The syncytiotrophoblast (STB), the outer layer of the human placenta, is vital to pregnancy health. STB is formed by cell fusion (syncytialization), whose proper maintenance is critical for pregnancy outcomes. HtrA4 is recently recognized as obligatory for syncytialization, including differentiation of trophoblast stem cells (TSCs) into STB, as HtrA4 knockdown (KD) inhibits the process. However, how HtrA4 facilitates syncytialization remains elusive. This study aimed to understand how HtrA4 is involved in syncytialization, by analyzing HtrA4-KD TSCs versus controls using mRNA transcriptomics and during STB differentiation. Our data revealed that HtrA4 is dispensable for initiation of this process, but is critically involved in many subsequent events of STB differentiation, including activation of signaling networks and re-structuring of the plasma membrane/cytoplasm/cytoskeleton/endomembrane system. Moreover, pathways related to nervous system development were suppressed during STB differentiation, and this was influenced by HtrA4. Furthermore, altering protein binding was identified as a major juncture of HtrA4 influence. Collectively, these findings confirming the pivotal role of HtrA4 in STB differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE334021 | GEO | 2026/09/13

REPOSITORIES: GEO