title: Bmi-1 Regulates Extensive Erythroid Self-Renewal.
abstract: Red blood cells (RBCs), responsible for oxygen delivery and carbon dioxide exchange, are essential for our well-being. Alternative RBC sources are needed to meet the increased demand for RBC transfusions projected to occur as our population ages. We previously have discovered that erythroblasts derived from the early mouse embryo can self-renew extensively ex vivo for many months. To better understand the mechanisms regulating extensive erythroid self-renewal, global gene expression data sets from self-renewing and differentiating erythroblasts were analyzed and revealed the differential expression of Bmi-1. Bmi-1 overexpression conferred extensive self-renewal capacity upon adult bone-marrow-derived self-renewing erythroblasts, which normally have limited proliferative potential. Importantly, Bmi-1 transduction did not interfere with the ability of extensively self-renewing erythroblasts (ESREs) to terminally mature either in vitro or in vivo. Bmi-1-induced ESREs can serve to generate in vitro models of erythroid-intrinsic disorders and ultimately may serve as a source of cultured RBCs for transfusion therapy.
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Ah Ram
authors.initials: AR
authors.lastname: Kim
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jayme L
authors.initials: JL
authors.lastname: Olsen
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: England
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Fegan
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14611, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Delgadillo
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: McGrath
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kingsley
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14611, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Waugh
authors.affiliation: Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: james_palis@urmc.rochester.edu.
authors.forename: James
authors.initials: J
authors.lastname: Palis
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D004921:Erythropoietin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D014916:Whole-Body Irradiation
chemical_list: C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; D004921:Erythropoietin; D003907:Dexamethasone; D063150:Polycomb Repressive Complex 1