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E2F4 Modulates Differentiation and Gene Expression in Hematopoietic Progenitor Cells during Commitment to the Lymphoid Lineage¹

Megan E. Enos^*, Simona A. Bancos, Timothy Bushnell and Ian N. Crispe^2,*

^* Department of Microbiology and Immunology, and the David H Smith Center for Vaccine Biology and Immunology, Department of Environmental Medicine, Lung Biology and Disease Program, and Department of Pediatrics, Center for Pediatric Biomedical Research, The James P. Wilmot Cancer Center, University of Rochester, Rochester, NY 14620

The E2F4 protein is involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation. We analyzed the impact of E2F4 deficiency on early steps in mouse hematopoietic development, and found defects in early hematopoietic progenitor cells that were propagated through common lymphoid precursors to the B and T lineages. In contrast, the defects in erythromyeloid precursor cells were self-correcting over time. This suggests that E2F4 is important in early stages of commitment to the lymphoid lineage. The E2F4-deficient progenitor cells showed reduced expression of several key lymphoid-lineage genes, and overexpression of two erythromyeloid lineage genes. However, we did not detect effects on cell proliferation. These findings emphasize the significance of E2F4 in controlling gene expression and cell fate.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant R01GM056689 from the National Institutes of Health (to I.N.C.).

² Address correspondence and reprint requests to Dr. Ian N. Crispe, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14620. E-mail address: Nick_Crispe{at}urmc.rochester.edu

³ Abbreviations used in this paper: HSC, hematopoietic stem cell; LSK, Lin^–sca-1⁺c-kit⁺; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; GMP, granulocyte-macrophage progenitor; MEP, megakaryocyte-erythroid progenitor; DN, double negative; WT, wild type.