Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner

Matthias Kieslinger, Silvia Hiechinger, Gergana Dobreva, G. Giacomo Consalez, Rudolf Grosschedl

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)496-507
Number of pages12
JournalCell Stem Cell
Volume7
Issue number4
DOIs
Publication statusPublished - Oct 8 2010

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

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