{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPOU5F1, which encodes the OCT4 protein, is a master transcription regulator that plays a central role in establishing and maintaining pluripotency and self‐renewal in embryonic stem cells. Early studies showed that OCT4, together with other key factors, activates a network of pluripotency‐associated genes and represses differentiation programs, thereby sustaining the undifferentiated state and enabling efficient reprogramming of somatic cells to induced pluripotent stem cells. OCT4 is essential not only during early embryogenesis but also for re‐establishing pluripotency in cell‐based reprogramming strategies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have revealed that the POU5F1 gene gives rise to several alternatively spliced transcripts and protein isoforms. Differential expression of the OCT4A isoform, which is restricted to pluripotent embryonic stem and embryonal carcinoma cells, versus OCT4B and other variants expressed in non‐pluripotent as well as differentiated cells, indicates that only specific isoforms confer the stemness properties central to early development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond normal development, aberrant or re‐activated expression of OCT4 has been documented in various cancers. In diverse tumor types – including bladder, oral, lung, rectal, ovarian, and head and neck cancers – OCT4 expression is associated with the acquisition of cancer stem cell properties, dedifferentiation, therapeutic resistance and enhanced tumorigenicity. These findings underscore that OCT4 not only orchestrates the maintenance of pluripotency in early embryonic cells but also may drive tumor progression by reactivating self‐renewal pathways in somatic cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOCT4 activity is further modulated by epigenetic and post‐translational mechanisms. For example, dynamic changes in cytosine methylation and histone modifications, as well as post‐translational modifications like sumoylation, contribute to the regulation of OCT4’s stability, DNA binding and transactivation potential. In certain contexts, factors such as Tet1 and FOXO1 have been shown to regulate OCT4 expression or even substitute functionally for it, thereby integrating OCT4 into broader regulatory circuits that govern cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐established roles in embryonic cells, OCT4 expression is also detected in various adult stem cell populations. Investigations in very small embryonic–like cells (VSELs), dental pulp stem cells, mesenchymal stem cells and even smooth muscle cells suggest that OCT4 contributes to the maintenance of stemness beyond early embryogenesis, and might be involved in cell plasticity and tissue regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, OCT4 plays pivotal roles during human embryogenesis. It is highly expressed in germ cells during early development and has been shown to be indispensable for proper blastocyst formation. Recent genome‐editing studies in human zygotes have demonstrated that loss of OCT4 function compromises blastocyst development, underscoring its essential role in early human development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maryam M Matin, James R Walsh, Paul J Gokhale, et al. 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