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Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E)
Abstract
The erythrocyte colony-forming unit (CFU-E) is a rare bone marrow (BM) progenitor that generates erythrocyte colonies in 48 hours. The existence of CFU-Es is based on these colonies, but CFU-Es have not been purified prospectively by phenotype. We have separated the “nonstem,” “nonlymphoid” compartment (lineage marker [lin]–c-Kit+Sca-1–IL-7Rα–) into interleukin 3 receptor α negative (IL-3Rα–) and IL-3Rα+ subsets. Within IL-3Rα– but not IL-3Rα+ cells we have identified TER119–CD41–CD71+ erythrocyte-committed progenitors (EPs). EPs generate CFU-E colonies at about 70% efficiency and generate reticulocytes in vivo. Depletion of EPs from BM strongly reduces CFU-E frequencies. EPs lack potential for erythrocyte burst-forming unit, megakaryocyte, granulocyte (G), and monocyte (M) colonies, and for spleen colony-forming units. Chronically suppressed erythropoiesis in interferon consensus sequence-binding protein (ICSBP)–deficient BM is associated with reduced frequencies of both the EP population and CFU-E colonies. During phenylhydrazine-induced acute anemia, numbers of both the EP population and CFU-E colonies increase. Collectively, EPs (lin–c-Kit+Sca-1–IL-7Rα–IL-3Rα–CD41–CD71+) account for most, if not all, CFU-E activity in BM. As a first molecular characterization, we have compared global gene expression in EPs and nonerythroid GM progenitors. These analyses define an erythroid progenitor-specific gene expression pattern. The prospective isolation of EPs is an important step to analyze physiologic and pathologic erythropoiesis.
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“The original definition of CMP (common myeloid progenitors) as myelo-erythroid restricted has largely rested on transplantation and colony assays, yet, it is unclear whether CMP function in this capacity physiologically15–18.”
From Polylox barcoding reveals haematopoietic stem cell fates realized in vivo (2017) · cites this paper as [16]
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Cited by
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Polylox barcoding reveals haematopoietic stem cell fates realized in vivo
Pei, W., Feyerabend, T. B., Rössler, J., Wang, X., Postrach, D., Busch, K., Rode, I., Klapproth, K., Dietlein, N., Quedenau, C., et al. (2017) · Nature · doi:10.1038/nature23653 · Cited by 443
Self-citationThe Branching Point in Erythro-Myeloid Differentiation
Perié, L., Duffy, K. R., Kok, L., de Boer, R. J., & Schumacher, T. N. (2015) · Cell · doi:10.1016/j.cell.2015.11.059 · Cited by 185
Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia
Ridinger-Saison, M., Evanno, E., Gallais, I., Rimmelé, P., Selimoglu-Buet, D., Sapharikas, E., Moreau-Gachelin, F., & Guillouf, C. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.88 · Cited by 34
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Metadata
- Authors
- Terszowski, G., Waskow, C., Conradt, P., Lenze, D., Koenigsmann, J., Carstanjen, D., Horak, I., & Rodewald, H.-R.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-01
- Volume
- 105
- Issue
- 5
- Pages
- 1937-1945
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 76
- References
- 3
- Language
- en
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