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Early B Cell Factor 2 Regulates Hematopoietic Stem Cell Homeostasis in a Cell-Nonautonomous Manner

By M. Kieslinger, S. Hiechinger, G. Dobreva, G. Consalez and R. Grosschedl

Abstract

Hematopoiesis requires the interaction of hematopoietic stem cells (HSCs) with various stromal microenvironments. Here, we examine the role of early B cell factor 2 (Ebf2), a transcription factor expressed in a subset of immature osteoblastic cells. Ebf2<sup>-/-</sup> mice show decreased frequencies of HSCs and lineage-committed progenitors. This defect is cell nonautonomous, as shown by the fact that transplantation of Ebf2-deficient bone marrow into wild-type hosts results in normal hematopoiesis. In coculture experiments, Ebf2<sup>-/-</sup> osteoblastic cells have reduced potential to support short-term proliferation of HSCs. Expression profiling of sorted Ebf2<sup>-/-</sup> osteoblastic cells indicated that several genes implicated in the maintenance of HSCs are downregulated relative to Ebf2<sup>+/-</sup> cells, whereas genes encoding secreted frizzled-related proteins are upregulated. Moreover, wild-type HSCs cocultured with Ebf2<sup>-/-</sup> osteoblastic cells show a reduced Wnt response relative to coculture with Ebf2<sup>+/-</sup> cells. Thus, Ebf2 acts as a transcriptional determinant of an osteoblastic niche that regulates the maintenance of hematopoietic progenitors, in part by modulating Wnt signaling

Year: 2010
OAI identifier: oai:escidoc.org:escidoc:2349091
Provided by: MPG.PuRe
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