BMP4 regulates the hematopoietic stem cell niche
Open Access
- 12 November 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 114 (20), 4393-4401
- https://doi.org/10.1182/blood-2009-02-206433
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.Keywords
This publication has 39 references indexed in Scilit:
- Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesisMechanisms of Development, 2009
- Disruption of BMP Signaling in Osteoblasts Through Type IA Receptor (BMPRIA) Increases Bone MassJournal of Bone and Mineral Research, 2008
- Endothelial Bmp4 Is Induced During Arterial Remodeling: Effects on Smooth Muscle Cell Migration and ProliferationJournal of Surgical Research, 2008
- Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Bone morphogenetic protein 4 modulates c‐Kit expression and differentiation potential in murine embryonic aorta‐gonad‐mesonephros haematopoiesis in vitroBritish Journal of Haematology, 2007
- Smad4 is critical for self-renewal of hematopoietic stem cellsThe Journal of Experimental Medicine, 2007
- Myeloid lineage progenitors give rise to vascular endotheliumProceedings of the National Academy of Sciences of the United States of America, 2006
- Bone Morphogenetic ProteinsGrowth Factors, 2004
- Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodelingProceedings of the National Academy of Sciences of the United States of America, 2004
- An essential role of Bmp4 in the atrioventricular septation of the mouse heartGenes & Development, 2003