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Open Access Green as soon as Postprint is submitted to ZB.
Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner.
Cell Stem Cell 7, 496-507 (2010)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Frizzledd-related protein-1; Bone-marrow; Beta-catenin; Self-renewal; Long-term; In-vivo; Lymphoid progenitors; Signaling center; Gamma-catenin; Niche
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
1934-5909
e-ISSN
1875-9777
Journal
Cell Stem Cell
Quellenangaben
Volume: 7,
Issue: 4,
Pages: 496-507
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-551200-001
PubMed ID
20887955
Scopus ID
77957326036
Erfassungsdatum
2010-11-22