The Corepressor Rcor1 Is Essential for Normal Myeloerythroid Lineage Differentiation. (14th July 2015)

• Record Type: Journal Article
• Authors: Yao, Huilan; Goldman, Devorah C.; Fan, Guang; Mandel, Gail; Fleming, William H.
• Is Part Of: Stem cells. Volume 33:Number 11(2015:Nov.)
• Page Start: 3304
• Page End: 3314
• Publication Date: 2015-07-14
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2086
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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 <italic>Rcor1</italic> 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, <italic>Rcor1<sup>−</sup><sup>/</sup><sup>−</sup></italic> monocytes exhibited extensive, cytokine‐dependent self‐renewal and overexpressed genes associated with hematopoietic stem/progenitor cell expansion including <italic>Gata2</italic>, <italic>Meis1</italic>, and <italic>Hoxa9</italic>. 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. S<sc>tem</sc> C<sc>ells</sc><italic>2015;33:3304–3314</italic></p> </abstract>