biostudies-literatureMcGrath KENCATS NIH HHSNIDDK NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases7619https://www.ebi.ac.uk/biostudies/studies/S-EPMC12356964biostudies-literatureUnknown16(1)The limited proliferative capacity of erythroid precursors is a major obstacle to generate sufficient in vitro-derived red blood cells for clinical purposes. While BMI1, a Polycomb Repressive Complex 1 member, is both necessary and sufficient to drive extensive proliferation of self-renewing erythroblasts, its mechanism of action remains poorly understood. Here we report that BMI1 overexpression leads to 10 billion-fold increase in self-renewal of human erythroblasts, which can terminally mature and agglutinate with typing reagent monoclonal antibodies. BMI1 and RING1B occupancy, along with repressive histone marks, are present at known BMI1 target genes, including the INK-ARF locus, consistent with altered cell cycle kinetics following BMI1 inhibition. Upregulation of BMI1 target genes wiNature communicationsBMI1 regulates human erythroid self-renewal through both gene repression and gene activation.PMC12356964UL1 TR002001DK124777U01 HL134696R01 DK104920R01 HL130670DK104920R01 DK124777R35 HL171168U54 DK106857Koniski ADWesthoff CMMcGrath KECarlson TLBlanc LKingsley PDSteiner LASchulz VPGallagher PGPalis JAn HHMurphy KEKim ARGetman MPapoin JZhang BChou STOlsen JLfalseBMI1 regulates human erythroid self-renewal through both gene repression and gene activation.The limited proliferative capacity of erythroid precursors is a major obstacle to generate sufficient in vitro-derived red blood cells for clinical purposes. While BMI1, a Polycomb Repressive Complex 1 member, is both necessary and sufficient to drive extensive proliferation of self-renewing erythroblasts, its mechanism of action remains poorly understood. Here we report that BMI1 overexpression leads to 10 billion-fold increase in self-renewal of human erythroblasts, which can terminally mature and agglutinate with typing reagent monoclonal antibodies. BMI1 and RING1B occupancy, along with repressive histone marks, are present at known BMI1 target genes, including the INK-ARF locus, consistent with altered cell cycle kinetics following BMI1 inhibition. Upregulation of BMI1 target genes wi2025-01-01T00:00:00Z2025 Aug2026-07-15T12:39:50.005Z2026-07-04T03:14:35.755ZS-EPMC123569644081709310.1038/s41467-025-62993-3