Genomics,Multiomics

Dataset Information

3

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


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 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, HSCs from Ebf2-/- mice and wild-type HSCs cocultured with Ebf2-/- osteoblastic cells show reduced Wnt responses. Thus, Ebf2 acts as a transcriptional determinant of an osteoblastic niche that regulates the maintenance of hematopoietic progenitors, in part by modulating Wnt signaling. Osteoblastic cells from tibia and femur of Ebf2 heterozygous and knockout mice (n=3 each) were loaded with FDG, FACS sorted and total RNA was isolated. cDNA was synthesised using the One-Cycle cDNA Synthesis Kit (Affymetrix), and labeled cRNA was synthesized by transcription in vitro, using the IVT labelling kit (Affymetrix). The labeled RNA was fragmented and hybridized to GeneChip® Mouse genome 430 2.0 arrays (GPL1261), according to the manufacturer’s instructions.

OTHER RELATED OMICS DATASETS IN: PRJNA125869

ORGANISM(S): Mus musculus domesticus  

SUBMITTER: Matthias Kieslinger   Gergana Dobreva  Giacomo Consalez  Rudolf Grosschedl  Silvia Hiechinger  Rudolf Grosschedl 

PROVIDER: E-GEOD-21700 | ArrayExpress | 2011-04-26

SECONDARY ACCESSION(S): GSE21700PRJNA125869

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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Action DRS
E-GEOD-21700.idf.txt Idf
E-GEOD-21700.processed.1.zip Processed
E-GEOD-21700.raw.1.zip Raw
E-GEOD-21700.sdrf.txt Txt
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Publications

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

Kieslinger Matthias M   Hiechinger Silvia S   Dobreva Gergana G   Consalez G Giacomo GG   Grosschedl Rudolf R  

Cell stem cell 20101001 4


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 c  ...[more]

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