p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells.
This study investigates the role of p38 mitogen-activated protein kinase (MAPK) as a critical regulator of reprogramming in mouse migratory primordial germ cells (PGCs). Mammalian germ cells, derived from PGCs, ensure species continuity through generations. In contrast to the irreversible commitment observed in mature germ cells, migratory PGCs exhibit a latent pluripotency capable of somatic differentiation and teratoma formation when misplaced, without necessitating exogenous repro-gramming factors. Our findings reveal that inhibition of p38 MAPK in mouse migratory PGCs enables the derivation of chemically induced Embryonic Germ-like Cells (cEGLCs), demonstrating naÃ¯ve plu-ripotency, chimera formation potential, and independence from conventional growth factors like LIF and FGF2. This independence suggests a unique signaling pathway involvement, distinct from conventional embryonic stem cells and embryonic germ cells. Moreover, cEGLCs display epiblast-like characteristics not typically associated with naÃ¯ve pluripotency, suggesting a nuanced pluripotent state that may reflect an early embryonic stage. This study establishes p38 MAPK as a gatekeeper in PGC fate, where its inhibition prompts a shift towards pluripotency, underscoring the enzyme's role in preventing unscheduled pluripotency and teratoma formation. The research highlights the significance of p38 MAPK in controlling the balance between proliferation and apoptosis, further implicating its function in germ cell development and differentiation. By elucidating the molecular underpinnings of PGC reprogramming, this work advances our understanding of germ cell biology, with implications for regenerative medicine and reproductive technologies. It suggests potential therapeutic targets for controlling pluripotency and offers insights into the mechanisms governing cell fate decisions in mammalian germ cells.