BMP4 regulates the hematopoietic stem cell niche

Devorah Goldman, Alexis S. Bailey, Dana L. Pfaffle, Azzah Al Masri, Jan L. Christian, William Fleming

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Bone morphogenetic protein 4 (BMP4) is required for mesoderm commitment to the hematopoietic lineage during early embryogenesis. However, deletion of BMP4 is early embryonically lethal and its functional role in definitive hematopoiesis is unknown. Consequently, we used a BMP4 hypomorph to investigate the role of BMP4 in regulating hematopoietic stem cell (HSC) function and maintaining steady-state hematopoiesis in the adult. Reporter gene expression shows that Bmp4 is expressed in cells associated with the hematopoietic microenvironment including osteoblasts, endothelial cells, and megakaryocytes. Although resting hematopoiesis is normal in a BMP4-deficient background, the number of c-Kit+, Sca-1+, Lineage- cells is significantly reduced. Serial transplantation studies reveal that BMP4-deficient recipients have a microenvironmental defect that reduces the repopulating activity of wild-type HSCs. This defect is even more pronounced in a parabiosis model that demonstrates a profound reduction in wild-type hematopoietic cells within the bone marrow of BMP4-deficient recipients. Furthermore, wild-type HSCs that successfully engraft into the BMP4-deficient bone marrow show a marked decrease in functional stem cell activity when tested in a competitive repopulation assay. Taken together, these findings indicate BMP4 is a critical component of the hematopoietic microenvironment that regulates both HSC number and function.

Original languageEnglish (US)
Pages (from-to)4393-4401
Number of pages9
JournalBlood
Volume114
Issue number20
DOIs
StatePublished - Nov 12 2009

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Bone Morphogenetic Protein 4
Stem Cell Niche
Hematopoietic Stem Cells
Stem cells
Hematopoiesis
Bone
Parabiosis
Defects
Megakaryocytes
Osteoblasts
Endothelial cells
Mesoderm
Reporter Genes
Gene expression
Embryonic Development
Assays
Stem Cells
Endothelial Cells
Cell Count
Transplantation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Goldman, D., Bailey, A. S., Pfaffle, D. L., Al Masri, A., Christian, J. L., & Fleming, W. (2009). BMP4 regulates the hematopoietic stem cell niche. Blood, 114(20), 4393-4401. https://doi.org/10.1182/blood-2009-02-206433

BMP4 regulates the hematopoietic stem cell niche. / Goldman, Devorah; Bailey, Alexis S.; Pfaffle, Dana L.; Al Masri, Azzah; Christian, Jan L.; Fleming, William.

In: Blood, Vol. 114, No. 20, 12.11.2009, p. 4393-4401.

Research output: Contribution to journalArticle

Goldman, D, Bailey, AS, Pfaffle, DL, Al Masri, A, Christian, JL & Fleming, W 2009, 'BMP4 regulates the hematopoietic stem cell niche', Blood, vol. 114, no. 20, pp. 4393-4401. https://doi.org/10.1182/blood-2009-02-206433
Goldman D, Bailey AS, Pfaffle DL, Al Masri A, Christian JL, Fleming W. BMP4 regulates the hematopoietic stem cell niche. Blood. 2009 Nov 12;114(20):4393-4401. https://doi.org/10.1182/blood-2009-02-206433
Goldman, Devorah ; Bailey, Alexis S. ; Pfaffle, Dana L. ; Al Masri, Azzah ; Christian, Jan L. ; Fleming, William. / BMP4 regulates the hematopoietic stem cell niche. In: Blood. 2009 ; Vol. 114, No. 20. pp. 4393-4401.
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