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Blood. 2014 May 15;123(20):3175-84. doi: 10.1182/blood-2013-11-538678. Epub 2014 Mar 20.

Corepressor Rcor1 is essential for murine erythropoiesis.

Author information

1
Vollum Institute.
2
Department of Pediatrics, Oregon Stem Cell Center, Knight Cancer Institute.
3
Oregon Clinical and Translational Research Institute.
4
Knight Cancer Institute, Oregon Clinical and Translational Research Institute, Division of Bioinformatics and Computational Biology.
5
Knight Cancer Institute, Department of Cell and Developmental Biology.
6
Department of Pathology, Oregon Health & Science University, Portland, OR;
7
Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA;
8
Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA; Howard Hughes Medical Institute, Boston, MA; and.
9
Vollum Institute, Howard Hughes Medical Institute, Portland, OR.

Abstract

The corepressor Rcor1 has been linked biochemically to hematopoiesis, but its function in vivo remains unknown. We show that mice deleted for Rcor1 are profoundly anemic and die in late gestation. Definitive erythroid cells from mutant mice arrest at the transition from proerythroblast to basophilic erythroblast. Remarkably, Rcor1 null erythroid progenitors cultured in vitro form myeloid colonies instead of erythroid colonies. The mutant proerythroblasts also aberrantly express genes of the myeloid lineage as well as genes typical of hematopoietic stem cells (HSCs) and/or progenitor cells. The colony-stimulating factor 2 receptor β subunit (Csf2rb), which codes for a receptor implicated in myeloid cytokine signaling, is a direct target for both Rcor1 and the transcription repressor Gfi1b in erythroid cells. In the absence of Rcor1, the Csf2rb gene is highly induced, and Rcor1(-/-) progenitors exhibit CSF2-dependent phospho-Stat5 hypersensitivity. Blocking this pathway can partially reduce myeloid colony formation by Rcor1-deficient erythroid progenitors. Thus, Rcor1 promotes erythropoiesis by repressing HSC and/or progenitor genes, as well as the genes and signaling pathways that lead to myeloid cell fate.

PMID:
24652990
PMCID:
PMC4023423
DOI:
10.1182/blood-2013-11-538678
[Indexed for MEDLINE]
Free PMC Article
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