First Author | Kieslinger M | Year | 2010 |
Journal | Cell Stem Cell | Volume | 7 |
Issue | 4 | Pages | 496-507 |
PubMed ID | 20887955 | Mgi Jnum | J:165655 |
Mgi Id | MGI:4837972 | Doi | 10.1016/j.stem.2010.07.015 |
Citation | Kieslinger M, et al. (2010) Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner. Cell Stem Cell 7(4):496-507 |
abstractText | 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. |