Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner.
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.
Kieslinger
Matthias
M
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology, 79108 Freiburg, Germany. matthias.kieslinger@helmholtz-muenchen.de
Hiechinger
Silvia
S
Dobreva
Gergana
G
Consalez
G Giacomo
GG
Grosschedl
Rudolf
R
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; C489922:Ebf2 protein, mouse