Author: ["Tim Ahfeldt","Robert T. Schinzel","Youn-Kyoung Lee","David Hendrickson","Adam Kaplan","David H. Lum","Raymond Camahort","Fang Xia","Jennifer Shay","Eugene P. Rhee","Clary B. Clish","Rahul C. Deo","Tony Shen","Frank H. Lau","Alicia Cowley","Greg Mowrer","Heba Al-Siddiqi","Matthias Nahrendorf","Kiran Musunuru","Robert E. Gerszten","John L. Rinn","Chad A. Cowan"]
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Abstract
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%–90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease. Cowan and colleagues have developed a method to efficiently differentiate human pluripotent stem cells into functional white or brown adipocytes, through the transient expression of PPARG2 alone or in combination with CEBP and PRDM16. The programmed cells are able to give rise to ectopic fat pads with white or brown adipose tissue characteristics.Cite this article
Ahfeldt, T., Schinzel, R., Lee, YK. et al. Programming human pluripotent stem cells into white and brown adipocytes. Nat Cell Biol 14, 209–219 (2012). https://doi.org/10.1038/ncb2411 