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Cell Stem Cell. 2010 Oct 8;7(4):496-507. doi: 10.1016/j.stem.2010.07.015.

Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner.

Author information

1
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology, 79108 Freiburg, Germany. matthias.kieslinger@helmholtz-muenchen.de

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(-/-) 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(-/-) osteoblastic cells have reduced potential to support short-term proliferation of HSCs. Expression profiling of sorted Ebf2(-/-) osteoblastic cells indicated that several genes implicated in the maintenance of HSCs are downregulated relative to Ebf2(+/-) cells, whereas genes encoding secreted frizzled-related proteins are upregulated. Moreover, wild-type HSCs cocultured with Ebf2(-/-) osteoblastic cells show a reduced Wnt response relative to coculture with Ebf2(+/-) 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.

PMID:
20887955
DOI:
10.1016/j.stem.2010.07.015
[Indexed for MEDLINE]
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