title: Searching for Classical Brown Fat in Humans: Development of a Novel Human Fetal Brown Stem Cell Model.
abstract: The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited extension in adult humans of brown depots, which are dramatically reduced after birth, solid cell models to study human brown adipogenesis and its regulatory factors in pathophysiology are urgently needed. Here, we generated a novel human model of brown adipose stem cells, hfB-ASC, derived for the first time from fetal interscapular brown fat depots. Besides the characterization of their stem and classical brown adipose properties, we demonstrated that these cells retain a specific intrinsic differentiation program to functional brown adipocytes, even spontaneously generating organoid structures with brown features. Moreover, for the first time, we investigated the thermogenic and electrophysiological activity of the in vitro-derived fetal brown adipocytes compared to their undifferentiated precursors hfB-ASC, in basal and norepinephrine-induced conditions. In conclusion, from interscapular brown fat of the human fetus we developed and functionally characterized a novel physiological brown adipose stem cell model early programmed to brown differentiation, which may represent a unique opportunity for further studies on brown adipogenesis processes in humans as well as the most suitable target to study novel therapeutic approaches for stimulating brown activity in metabolic pathologies. Stem Cells 2016;34:1679-1691.
authors: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Italy.
authors: Alessandra
authors: A
authors: Di Franco
authors: Department of Experimental and Clinical Medicine, Histology and Embryology Unit, University of Florence, Italy.
authors: Daniele
authors: D
authors: Guasti
authors: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Italy.
authors: Roberta
authors: R
authors: Squecco
authors: Department of Experimental and Clinical Medicine, Haematology Unit, University of Florence, Italy.
authors: Benedetta
authors: B
authors: Mazzanti
authors: Italian National Research Council, Institute of Applied Physics, Sesto Fiorentino, Italy.
authors: Francesca
authors: F
authors: Rossi
authors: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Italy.
authors: Eglantina
authors: E
authors: Idrizaj
authors: Departament de Bioquimica i Biologia Molecular, Institute of Biomedicine, University of Barcelona, and Centro de Investigación Biomédica en Red Fisiopatologia de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: José M
authors: JM
authors: Gallego-Escuredo
authors: Departament de Bioquimica i Biologia Molecular, Institute of Biomedicine, University of Barcelona, and Centro de Investigación Biomédica en Red Fisiopatologia de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Villarroya
authors: Department of Experimental and Clinical Medicine, Histology and Embryology Unit, University of Florence, Italy.
authors: Daniele
authors: D
authors: Bani
authors: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Italy.
authors: Gianni
authors: G
authors: Forti
authors: Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.
authors: Gabriella Barbara
authors: GB
authors: Vannelli
authors: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Italy.
authors: Michaela
authors: M
authors: Luconi
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000328:Adult; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D055724:Electrophysiological Phenomena; D053686:Fetal Stem Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008954:Models, Biological; D009940:Organoids / Q000166:cytology; D010641:Phenotype; D013817:Thermography
keywords: Adipogenesis; Brown adipocytes; Cell electrophysiology; Stem cells; UCP-1