FOXM1 Maintains Homeostasis and Self-Renewal in Wharton's Jelly Mesenchymal Stem Cells

The transcription factor FOXM1 is a master regulator of the cell cycle and is implicated in various cell fate decisions. However, its functional role and regulatory network in human Wharton's jelly mesenchymal stem cells (WJ-MSCs) remain poorly defined. This study aimed to elucidate the comprehensive function of FOXM1 in maintaining WJ-MSC stemness, proliferation, and survival, and to delineate the underlying molecular mechanisms.

We used RNA Interference to knock down FOXM1 in WJ-MSCs. The phenotypic impacts were assessed through CCK-8, colony formation, migration, and flow cytometry assays. We analyzed transcriptomic changes using RNA-seq and verified the results through qRT-PCR and Western blotting.

Knockdown of FOXM1 significantly reduced the expression of core pluripotency factors (OCT4, SOX2, and NANOG), impairing stem cell identity and abolishing colony formation and migration capacities. Furthermore, FOXM1 deficiency induced G0/G1 phase cell cycle arrest, downregulated CCND1, and triggered apoptosis through a mechanism involving p53 accumulation, an increased BAX/BCL-2 ratio, and Caspase-3 activation. RNA-seq analysis further corroborated the systematic downregulation of cell cycle pathways and upregulation of apoptotic pathways upon FOXM1 deficiency.

Our findings establish FOXM1 as a critical regulatory node that integrates stem cell identity with proliferative and survival signals to maintain WJ-MSC homeostasis. This study redefines FOXM1's role in stem cell biology and provides a theoretical foundation for enhancing the therapeutic efficacy of WJ-MSCs by modulating this key factor.