Identification of adiponectin as a novel hemopoietic stem cell growth factor

Leah DiMascio, Carlijn Voermans, Mweia Uqoezwa, Andrew Duncan, Danhong Lu, Judy Wu, Uma Sankar, Tannishtha Reya

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3511-3520
Number of pages10
JournalJournal of Immunology
Volume178
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    DiMascio, L., Voermans, C., Uqoezwa, M., Duncan, A., Lu, D., Wu, J., Sankar, U., & Reya, T. (2007). Identification of adiponectin as a novel hemopoietic stem cell growth factor. Journal of Immunology, 178(6), 3511-3520. https://doi.org/10.4049/jimmunol.178.6.3511