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Published online before print May 3, 2004

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(Journal of Leukocyte Biology. 2004;76:484-490.)
© 2004 by Society for Leukocyte Biology

Increased numbers of committed myeloid progenitors but not primitive hematopoietic stem/progenitors in mice lacking STAT6 expression

Kevin D. Bunting^*,,1, Wen-Mei Yu^*, Heath L. Bradley^*, Eleonora Haviernikova^*, Ann E. Kelly-Welch, Achsah D. Keegan^, and Cheng-Kui Qu^*,,1

^* Departments of Hematopoiesis and
Immunology, American Red Cross, Jerome H. Holland Laboratory for the Biomedical Sciences, Rockville, Maryland; and Departments of
Anatomy and Cell Biology and
Immunology, The George Washington University, Washington, D.C.

¹Correspondence: Hematopoiesis Department, American Red Cross, Jerome H. Holland Laboratory for the Biomedical Sciences, 15601 Crabbs Branch Way, Rockville, MD 20855. E-mail: quc{at}usa.redcross.org or buntingk{at}usa.redcross.org

Signal transducer and activator of transcription-6 (STAT6) plays important roles in cytokine signaling via interleukin-4 and -13 receptors (IL-4R and IL-13R). Mice in which STAT6 has been disrupted by homologous recombination show defects in T helper cell type 2 (Th2) lymphocyte production, resulting in an accumulation of Th1 cells. In addition to defects in differentiation and proliferation of T lymphocytes, STAT6-deficient mice show increased cell-cycle activation and frequency of myeloid progenitors. Although this has been shown to be mediated through Oncostatin M production by T cells, IL-4R and STAT6 have also recently been found to be enriched for expression in primitive hematopoietic stem cells (HSCs) in gene expression-profiling studies. Therefore, we have investigated whether defects in hematopoietic function in mice lacking STAT6 expression extended into the primitive hematopoietic compartments of the bone marrow. Here, we report that STAT6 deficiency increased bone marrow-committed myeloid progenitors but did not alter the number of cells enriched for HSC/multipotent progenitors, primitive cobblestone area-forming cells assayed in vitro, or bone marrow short-term or long-term repopulating cells assayed in vivo. Therefore, the requirement for STAT6 activation during hematopoiesis is limited, and primitive hematopoietic cell types are insulated against possible effects of cytokine stimulation by Th1 cells.

Key Words: interleukin-4 • knockout mouse • hematopoietic stem cell • hematopoiesis

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