IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells

Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31−/34+/146− cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor‐1 (IGF1) promoted a lineage bias tow...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2015-08, Vol.33 (8), p.2483-2495
Main Authors: Hu, Li, Yang, Guodong, Hägg, Daniel, Sun, Guoming, Ahn, Jeffrey M., Jiang, Nan, Ricupero, Christopher L., Wu, June, Rodhe, Christine Hsu, Ascherman, Jeffrey A., Chen, Lili, Mao, Jeremy J.
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipogenesis
Adipose
Adipose tissue
Adult
Animals
Antigens, Differentiation - metabolism
Axin2
Bias
CD146
Cell Differentiation
Female
Humans
Insulin growth factor‐1
Insulin-Like Growth Factor I - metabolism
Mesenchymal
Mice
Middle Aged
PPARγ
Stem cells
Stem Cells - metabolism
Stromal vascular fraction
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Summary:Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31−/34+/146− cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor‐1 (IGF1) promoted a lineage bias towards CD31−/34+/146− cells at the expense of CD31−/34+/146+ cells. IGF1 was microencapsulated in poly(lactic‐co‐glycolic acid) scaffolds and implanted in the inguinal fat pad of C57Bl6 mice. Control‐released IGF1 induced remarkable adipogenesis in vivo by recruiting endogenous cells. In comparison with the CD31−/34+/146+ cells, CD31−/34+/146− cells had a weaker Wnt/β‐catenin signal. IGF1 attenuated Wnt/β‐catenin signaling by activating Axin2/PPARγ pathways in SVF cells, suggesting IGF1 promotes CD31−/34+/146− bias through tuning Wnt signal. PPARγ response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPARγ transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPARγ axis in adipogenesis that is particularly attributable to a lineage bias towards CD31−/34+/146− cells, with implications in adipose regeneration. Stem Cells 2015;33:2483–2495
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.2052