PPARgamma-dependent and PPARgamma-independent effects on the development of adipose cells from embryonic stem cells.
Peroxisome proliferator-activated receptor (PPAR) gamma was shown to be required for adipocyte formation both in vivo and in vitro. However, the role of PPARgamma in the initial steps of adipose cell development was not distinguished from its role in the terminal steps. We now show that PPARgamma is expressed early in embryoid bodies (EBs) derived from embryonic stem cells and in E.8.5 mouse embryos. Addition of a specific ligand for PPARgamma in developing EBs over-expressing PPARgamma did not commit stem cells towards the adipose lineage. In differentiated PPARgamma(-/-) EBs, only markers characteristic of preadipocytes were found to be expressed. PPARdelta is present in EBs but did not compensate for the lack of PPARgamma in terminal differentiation. Taken together, these results favor a critical PPARgamma-independent phase culminating in preadipocyte formation that precedes a PPARgamma-dependent phase in the development of adipose cells from pluripotent stem cells.
Vernochet
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C
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre du Biochimie, 06108 Nice Cedex 2, France.
Milstone
D S
DS
Iehlé
C
C
Belmonte
N
N
Phillips
B
B
Wdziekonski
B
B
Villageois
P
P
Amri
E Z
EZ
O'Donnell
P E
PE
Mortensen
R M
RM
Ailhaud
G
G
Dani
C
C
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D015870:Gene Expression; D025743:HMGA2 Protein / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
D015415:Biomarkers; D025743:HMGA2 Protein; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D014212:Tretinoin; D008071:Lipoprotein Lipase