Differentiation of human induced pluripotent stem cells into brown and white adipocytes: Role of Pax3.

: Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown and white adipocyte progenitors (APs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here we report a procedure to selectively derive brown and white APs from human induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9 and HoxA5 genes were specifically expressed in white APs, whereas expression of PRDM16, Dio2 and Pax3 marked brown APs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert white APs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human brown APs and a molecular mediator of their fate. The findings of the present study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes. Stem Cells 2013.