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Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E)

Terszowski, Grzegorz, Waskow, Claudia, Conradt, Peter, Lenze, Dido, Koenigsmann, Jessica, Carstanjen, Dirk, Horak, Ivan, Rodewald, Hans-Reimer·2005·Blood

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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Metadata

Authors
Terszowski, G., Waskow, C., Conradt, P., Lenze, D., Koenigsmann, J., Carstanjen, D., Horak, I., & Rodewald, H.-R.
Venue
Blood
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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Terszowski, G., Waskow, C., Conradt, P., Lenze, D., Koenigsmann, J., Carstanjen, D., Horak, I., & Rodewald, H.-R. (2005). Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E). Blood. https://doi.org/10.1182/blood-2004-09-3459