Induction of germline-like cells (PGCLCs)

Abstract

Investigations into primordial germ cell-like cells (PGCLCs) constitute a rapidly evolving frontier in reproductive biology and regenerative medicine, offering transformative potential for both basic research and clinical applications. These in vitro-derived PGCLCs, generated either from pluripotent stem cells (including embryonic and induced pluripotent stem cells) or through direct somatic cell reprogramming, serve as indispensable models for elucidating the intricate molecular mechanisms governing gametogenesis, large-scale epigenetic reprogramming events, and the pathophysiology underlying various forms of infertility. Seminal advancements in this domain include the establishment of robust differentiation protocols employing critical signaling molecules such as bone morphogenetic proteins (BMPs), WNT pathway agonists, and retinoic acid derivatives, alongside innovative approaches involving direct lineage conversion of somatic cell types. Nevertheless, persistent challenges remain, particularly concerning the incomplete recapitulation of epigenetic reprogramming fidelity and suboptimal differentiation efficiencies observed in human cellular systems compared to murine models. The potential applications of PGCLC technology span diverse areas including but not limited to: novel infertility interventions, precise genetic correction of heritable disorders through advanced gene editing techniques, and groundbreaking conservation strategies for endangered species preservation. Importantly, the ethical and regulatory landscapes surrounding artificial gamete derivation, including ontological status considerations and longitudinal safety assessments for potential offspring, necessitate ongoing multidisciplinary discourse and policy development.