title: Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat.
abstract: Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1(+)/CD45(-)/Mac1(-); referred to as Sca-1(+) progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1(+) cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.
authors.affiliation: The Joslin Diabetes Center, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA 02215, USA.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schulz
authors.forename: Tian Lian
authors.initials: TL
authors.lastname: Huang
authors.forename: Thien T
authors.initials: TT
authors.lastname: Tran
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Townsend
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shadrach
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cerletti
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: McDougall
authors.forename: Nino
authors.initials: N
authors.lastname: Giorgadze
authors.forename: Tamara
authors.initials: T
authors.lastname: Tchkonia
authors.forename: Denis
authors.initials: D
authors.lastname: Schrier
authors.forename: Dean
authors.initials: D
authors.lastname: Falb
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology
chemical_list: D000950:Antigens, Ly; D055419:Bone Morphogenetic Protein 7; C074650:Ly6a protein, mouse; D008565:Membrane Proteins