Bmi-1 Regulates Extensive Erythroid Self-Renewal
| Autor: | James Palis, Ah Ram Kim, Katherine H. Fegan, Luis F. Delgadillo, Jayme L. Olsen, Kathleen E. McGrath, Samantha J. England, Paul D. Kingsley, Richard E. Waugh, Yu-Shan Huang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Erythroblasts
Transgene Population Stem cell factor Mice Transgenic Mice SCID Biology Biochemistry Dexamethasone 03 medical and health sciences Transduction (genetics) Mice 0302 clinical medicine RNA interference Mice Inbred NOD Proto-Oncogene Proteins Report hemic and lymphatic diseases Gene expression Genetics Animals RNA Small Interfering education lcsh:QH301-705.5 Erythropoietin 030304 developmental biology Cell Proliferation Mice Knockout Polycomb Repressive Complex 1 0303 health sciences education.field_of_study lcsh:R5-920 Mice Inbred ICR Stem Cell Factor Cell growth Embryo hemic and immune systems Cell Biology 3. Good health Cell biology Mice Inbred C57BL lcsh:Biology (General) 030220 oncology & carcinogenesis Immunology RNA Interference lcsh:Medicine (General) Whole-Body Irradiation Developmental Biology circulatory and respiratory physiology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 4, Iss 6, Pp 995-1003 (2015) |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2015.05.003 |
| Popis: | Summary 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. Graphical Abstract Highlights • Bmi-1 promotes the extensive self-renewal of adult murine erythroblasts • Transfusion of iESRE leads to fully mature RBCs that circulate for 6–7 weeks in vivo Palis and colleagues determined that Bmi-1 is preferentially expressed in self-renewing erythroblasts and that Bmi-1 promotes the extensive self-renewal of erythroblasts derived from adult murine bone marrow, which normally have limited self-renewal capacity. Importantly, Bmi-1-induced self-renewing erythroblasts maintain their capacity to terminally mature into enucleated red cells both in vitro and in vivo. |
| Databáze: | OpenAIRE |
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