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

Kieslinger, M., Hiechinger, S., Dobreva, G., Consalez, G. G., & Grosschedl, R. (2010). Early B Cell Factor 2 Regulates Hematopoietic Stem Cell Homeostasis in a Cell-Nonautonomous Manner. Cell Stem Cell, 7, 496-507. doi:10.1016/j.stem.2010.07.015.

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Kieslinger, Matthias1, Author              
Hiechinger, Silvia2, Author
Dobreva, Gergana1, Author              
Consalez, G. Giacomo2, Author
Grosschedl, Rudolf1, Author              
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1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              

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 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.

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Language(s): eng - English
 Dates: 2010-10-08
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.stem.2010.07.015
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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 7 Sequence Number: - Start / End Page: 496 - 507 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909