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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation
  • Cell Lineage
  • Gene Expression Regulation
  • Hematopoiesis*
  • Hematopoietic Stem Cells / metabolism*
  • Mice
  • Mutation
  • Osteoblasts / cytology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Ebf2 protein, mouse

Associated data

  • GEO/GSE21700