The corepressor Rcor1 is essential for normal myeloerythroid lineage differentiation

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Based on its physical interactions with histone-modifying enzymes, the transcriptional corepressor Rcor1 has been implicated in the epigenetic regulation blood cell development. Previously, we have demonstrated that Rcor1 is essential for the maturation of definitive erythroid cells and fetal survival. To determine the functional role of Rcor1 in steady-state hematopoiesis in the adult, we used a conditional knockout approach. Here, we show that the loss of Rcor1 expression results in the rapid onset of severe anemia due to a complete, cell autonomous block in the maturation of committed erythroid progenitors. By contrast, both the frequency of megakaryocyte progenitors and their capacity to produce platelets were normal. Although the frequency of common lymphoid progenitors and T cells was not altered, B cells were significantly reduced and showed increased apoptosis. However, Rcor1-deficient bone marrow sustained normal levels of B-cells following transplantation, indicating a non-cell autonomous requirement for Rcor1 in B-cell survival. Evaluation of the myelomonocytic lineage revealed an absence of mature neutrophils and a significant increase in the absolute number of monocytic cells. Rcor1-deficient monocytes were less apoptotic and showed ∼100-fold more colony-forming activity than their normal counterparts, but did not give rise to leukemia. Moreover, Rcor1- / - monocytes exhibited extensive, cytokine-dependent self-renewal and overexpressed genes associated with hematopoietic stem/progenitor cell expansion including Gata2, Meis1, and Hoxa9. Taken together, these data demonstrate that Rcor1 is essential for the normal differentiation of myeloerythroid progenitors and for appropriately regulating self-renewal activity in the monocyte lineage.

Original languageEnglish (US)
Pages (from-to)3304-3314
Number of pages11
JournalStem Cells
Volume33
Issue number11
DOIs
StatePublished - Nov 1 2015

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Co-Repressor Proteins
Lymphoid Progenitor Cells
Monocytes
B-Lymphocytes
Hematopoietic Stem Cells
Cell Survival
Megakaryocyte Progenitor Cells
Erythroid Cells
Cell Transplantation
Hematopoiesis
Epigenomics
Histones
Anemia
Blood Cells
Leukemia
Neutrophils
Blood Platelets
Cell Count
Bone Marrow
Apoptosis

Keywords

  • Corepressor proteins
  • Epigenetics
  • Erythropoiesis
  • Hematopoiesis
  • Monocytes
  • Neutrophils

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

The corepressor Rcor1 is essential for normal myeloerythroid lineage differentiation. / Yao, Huilan; Goldman, Devorah; Fan, Guang; Mandel, Gail; Fleming, William.

In: Stem Cells, Vol. 33, No. 11, 01.11.2015, p. 3304-3314.

Research output: Contribution to journalArticle

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