A Renewable Source of Human Beige Adipocytes for Development of Therapies to Treat Metabolic Syndrome
Su Su,
Anyonya R. Guntur,
Daniel C. Nguyen,
Shameem S. Fakory,
Chad C. Doucette,
Cassandra Leech,
Humphrey Lotana,
Matthew Kelley,
Jaspreet Kohli,
Julieta Martino,
Sunder Sims-Lucas,
Lucy Liaw,
Calvin Vary,
Clifford J. Rosen,
Aaron C. Brown
Affiliations
Su Su
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Anyonya R. Guntur
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Daniel C. Nguyen
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Shameem S. Fakory
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Chad C. Doucette
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Cassandra Leech
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Humphrey Lotana
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Matthew Kelley
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Jaspreet Kohli
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
Julieta Martino
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA
Sunder Sims-Lucas
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA; UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
Lucy Liaw
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA
Calvin Vary
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA
Clifford J. Rosen
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA
Aaron C. Brown
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA; Corresponding author
Summary: Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF1+ mesoderm and progress through an expandable mural-like mesenchymal stem cell (MSC) to form mature beige adipocytes that display a thermogenically active profile. This includes expression of uncoupling protein 1 (UCP1) concomitant with increased uncoupled respiration. With this method, dysfunctional adipogenic precursors can be reprogrammed and differentiated into beige adipocytes with increased thermogenic function and anti-diabetic secretion potential. This resource can be used to (1) elucidate mechanisms that underlie the control of beige adipogenesis and (2) generate material for cellular-based therapies that target metabolic syndrome in humans. : Su et al. demonstrate a method for producing beige adipocytes from human induced pluripotent stem cells in a stepwise manner through defined precursor lineages. This renewable resource provides a developmental framework to study human beige adipogenesis and can be used to develop treatments for obesity-related disorders. Keywords: adipogenesis, beige adipocytes, UCP1, metabolic syndrome, diabetes, mesoderm
