title: Differentiation of human induced pluripotent stem cells into brown and white adipocytes: role of Pax3.
abstract: 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 (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs 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 WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. 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 WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this 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.
authors.affiliation: Université Nice Sophia Antipolis, iBV, UMR CNRS/INSERM, Faculté de Médecine, Nice Cedex, France.
authors.forename: Tala
authors.initials: T
authors.lastname: Mohsen-Kanson
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Hafner
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wdziekonski
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Phi
authors.initials: P
authors.lastname: Villageois
authors.forename: Audrey
authors.initials: A
authors.lastname: Carrière
authors.forename: Maria
authors.initials: M
authors.lastname: Svensson
authors.forename: Claude
authors.initials: C
authors.lastname: Bagnis
authors.forename: Bérengère
authors.initials: B
authors.lastname: Chignon-Sicard
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014212:Tretinoin
keywords: Adipocyte development; Adipocyte progenitors; Human induced pluripotent stem cells; Pax3