Received 22 June 2009; accepted 26 June 2009. published online 03 July 2009.
Objective
It has generally been believed that adipocytes are derived from mesenchymal stem cells via fibroblasts. We recently reported that fibroblasts/myofibroblasts in a number of tissues and organs are derived from hematopoietic stem cells (HSCs). In the present study, we tested the hypothesis that HSCs also give rise to adipocytes.
Materials and Methods
Using transplantation of a single enhanced green fluorescent protein−positive (EGFP+) HSC and primary culture, we examined generation of adipocytes from HSCs.
Results
Adipose tissues from clonally engrafted mice showed EGFP+ adipocytes that stained positive for leptin, perilipin, and fatty acid binding protein 4. A diet containing rosiglitazone, a peroxisome proliferator−activated receptor-γ agonist, significantly enhanced the number of EGFP+ adipocytes. When EGFP+ bone marrow cells from clonally engrafted mice were cultured under adipogenic conditions, all of the cultured cells stained positive with Oil Red O and Sudan Black B and exhibited the presence of abundant mRNA for adipocyte markers. Finally, clonal culture- and sorting-based studies of Mac-1 expression of hematopoietic progenitors suggested that adipocytes are derived from HSCs via progenitors for monocytes/macrophages.
Conclusion
Together, these studies clarify the current controversy regarding the ability of HSCs to give rise to adipocytes. Furthermore, our primary culture method that generates adipocytes from uncommitted hematopoietic cells should contribute to the studies of the mechanisms of early adipocytic differentiation and may lead to development of therapeutic solutions for many general obesity issues.
aDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC., USA
bResearch Services, Department of Veterans Affairs Medical Center, Charleston, SC., USA
cHollings Cancer Center, Medical University of South Carolina, Charleston, SC., USA
dDepartment of Medicine, Medical University of South Carolina, Charleston, SC., USA
Offprint requests to: Makio Ogawa, M.D., Ph.D., Department of Pathology and Laboratory Medicine Medical University of South Carolina, 109 Bee Street, Charleston, SC 29401
ABSTRACT