{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAccumulating evidence indicates that BMI1—a polycomb group transcriptional repressor—is a master regulator of stem cell self‐renewal and proliferative capacity across multiple tissues. In hematopoietic, neural, and intestinal stem cells, BMI1 preserves the long‐term repopulating potential by repressing critical cell cycle inhibitors (notably p16^INK4A and p19^ARF) that would otherwise trigger senescence, thereby ensuring sustained tissue homeostasis and regenerative competence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its key role in stem cell maintenance, BMI1 contributes to epigenetic regulation by participating in polycomb repressive complexes. Its activity promotes histone modifications—such as H2A ubiquitination—that silence developmental and differentiation‐associated genes (including Hox genes) and thereby help to frame cell identity during embryogenesis and adult tissue renewal."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of BMI1 is also implicated in tumorigenesis. Overexpression of BMI1 underlies the maintenance and enhanced proliferative potential of cancer stem and progenitor cells in hematologic malignancies, medulloblastoma, and gliomas, among others, by counteracting anti‐proliferative signals. Moreover, BMI1 acts as an epigenetic barrier during direct reprogramming of somatic cells, as its reduction can facilitate fate conversion through remodeling of chromatin marks (thereby increasing active H3K4me3 and reducing repressive H2AK119ub) and altering metabolic and redox states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies underscore the multifaceted roles of BMI1 in developmental biology and disease. By orchestrating epigenetic repression, promoting stem cell self‐renewal and proliferation, and modulating cellular metabolism, BMI1 emerges not only as a pivotal determinant of normal tissue maintenance but also as a central player in cancer progression and a potential therapeutic target for regenerative medicine and oncology interventions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julie Lessard, Guy Sauvageau "}, {"type": "b", "children": [{"type": "t", "text": "Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01572"}], "href": "https://doi.org/10.1038/nature01572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12714970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12714970"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "In-kyung Park, Dalong Qian, Mark Kiel, et al. 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