Hematopoietic stem cell origin of adipocytes.
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.


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-gamma 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.


CONCLUSIONS
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.
Sera
Yasuhiko
Y
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29401, USA.
LaRue
Amanda C
AC
Moussa
Omar
O
Mehrotra
Meenal
M
Duncan
James D
JD
Williams
Christopher R
CR
Nishimoto
Eishi
E
Schulte
Bradley A
BA
Watson
Patricia M
PM
Watson
Dennis K
DK
Ogawa
Makio
M
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004032:Diet; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020738:Leptin / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000819:agonists; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014184:Transplantation, Homologous
D000943:Antigens, Differentiation; D002352:Carrier Proteins; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D020738:Leptin; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone