title: De novo generation of adipocytes from circulating progenitor cells in mouse and human adipose tissue.
abstract: White adipocytes in adults are typically derived from tissue resident mesenchymal progenitors. The recent identification of de novo production of adipocytes from bone marrow progenitor-derived cells in mice challenges this paradigm and indicates an alternative lineage specification that adipocytes exist. We hypothesized that alternative lineage specification of white adipocytes is also present in human adipose tissue. Bone marrow from transgenic mice in which luciferase expression is governed by the adipocyte-restricted adiponectin gene promoter was adoptively transferred to wild-type recipient mice. Light emission was quantitated in recipients by in vivo imaging and direct enzyme assay. Adipocytes were also obtained from human recipients of hematopoietic stem cell transplantation. DNA was isolated, and microsatellite polymorphisms were exploited to quantify donor/recipient chimerism. Luciferase emission was detected from major fat depots of transplanted mice. No light emission was observed from intestines, liver, or lungs. Up to 35% of adipocytes in humans were generated from donor marrow cells in the absence of cell fusion. Nontransplanted mice and stromal-vascular fraction samples were used as negative and positive controls for the mouse and human experiments, respectively. This study provides evidence for a nontissue resident origin of an adipocyte subpopulation in both mice and humans.
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gavin
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Gutman
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Kohrt
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Shea
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Miller
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Sullivan
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Erickson
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Helm
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Alistaire S
authors.initials: AS
authors.lastname: Acosta
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Childs
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Musselwhite
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kelly
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Majka
authors.affiliation: *Division of Geriatric Medicine, Division of Medical Oncology, and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Flow Cytometry Shared Resource, Molecular Pathology/Cytogenetics Shared Resource, University of Colorado Cancer Center, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, and Colorado Obesity Research Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Molecular Diagnostic Laboratory, Children's Hospital Colorado, Aurora, Colorado, USA; and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and **Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA dwight.klemm@ucdenver.edu.
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Klemm
mesh_terms: D052438:Adipocytes, White / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002459:Cell Fusion / Q000379:methods; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
keywords: adipogenesis; bone marrow; polymorphic microsatellite; short tandem repeat; stem cell