Identification of adiponectin as a novel hemopoietic stem cell growth factor.
The hemopoietic microenvironment consists of a diverse repertoire of cells capable of providing signals that influence hemopoietic stem cell function. Although the role of osteoblasts and vascular endothelial cells has recently been characterized, the function of the most abundant cell type in the bone marrow, the adipocyte, is less defined. Given the emergence of a growing number of adipokines, it is possible that these factors may also play a role in regulating hematopoiesis. Here, we investigated the role of adiponectin, a secreted molecule derived from adipocytes, in hemopoietic stem cell (HSC) function. We show that adiponectin is expressed by components of the HSC niche and its receptors AdipoR1 and AdipoR2 are expressed by HSCs. At a functional level, adiponectin influences HSCs by increasing their proliferation, while retaining the cells in a functionally immature state as determined by in vitro and in vivo assays. We also demonstrate that adiponectin signaling is required for optimal HSC proliferation both in vitro and in long term hemopoietic reconstitution in vivo. Finally we show that adiponectin stimulation activates p38 MAPK, and that inhibition of this pathway abrogates adiponectin's proliferative effect on HSCs. These studies collectively identify adiponectin as a novel regulator of HSC function and suggest that it acts through a p38 dependent pathway.
DiMascio
Leah
L
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Voermans
Carlijn
C
Uqoezwa
Mweia
M
Duncan
Andrew
A
Lu
Danhong
D
Wu
Judy
J
Sankar
Uma
U
Reya
Tannishtha
T
D017667:Adipocytes / Q000502:physiology; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
D052242:Adiponectin; C499919:Adipoq protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D048051:p38 Mitogen-Activated Protein Kinases