title: Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose-derived stem cells.
abstract: Stem cell antigen-1 (Sca1 or Ly6A/E) is a cell surface marker that is widely expressed in mesenchymal stem cells, including adipose-derived stem cells (ASCs). We hypothesized that the fat depot-specific gene signature of Sca1(high) ASCs may play the major role in defining adipose tissue function and extracellular matrix (ECM) remodeling in a depot-specific manner. Herein we aimed to characterize the unique gene signature and ECM remodeling of Sca1(high) ASCs isolated from subcutaneous (inguinal) and visceral (epididymal) adipose tissues. Sca1(high) ASCs are found in the adventitia and perivascular areas of adipose tissues. Sca1(high) ASCs purified with magnetic-activated cell sorting (MACS) demonstrate dendrite or round shape with the higher expression of cytokines and chemokines (e.g., Il6, Cxcl1) and the lower expression of a glucose transporter (Glut1). Subcutaneous and visceral fat-derived Sca1(high) ASCs particularly differ in the gene expressions of adhesion and ECM molecules. While the expression of the major membrane-type collagenase (MMP14) is comparable between the groups, the expressions of secreted collagenases (MMP8 and MMP13) are higher in visceral Sca1(high) ASCs than in subcutaneous ASCs. Consistently, slow but focal MMP-dependent collagenolysis was observed with subcutaneous adipose tissue-derived vascular stromal cells, whereas rapid and bulk collagenolysis was observed with visceral adipose tissue-derived cells in MMP-dependent and -independent manners. These results suggest that the fat depot-specific gene signatures of ASCs may contribute to the distinct patterns of ECM remodeling and adipose function in different fat depots.
authors.affiliation: Department of Internal Medicine, Division of MEND, University of Michigan Medical School, United States.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Tokunaga
authors.affiliation: Department of Internal Medicine, Division of MEND, University of Michigan Medical School, United States.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine, Division of MEND, University of Michigan Medical School, United States; Biointerfaces Institute, University of Michigan, United States.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, Division of MEND, University of Michigan Medical School, United States; Biointerfaces Institute, University of Michigan, United States.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Barnes
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Buchner
authors.affiliation: Department of Internal Medicine, Division of MEND, University of Michigan Medical School, United States; Biointerfaces Institute, University of Michigan, United States. Electronic address: taehwa@med.umich.edu.
authors.forename: Tae-Hwa
authors.initials: TH
authors.lastname: Chun
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins
keywords: Adipocyte; Adipose-derived stem cell; Collagen; ECM; MMP; Obesity; RNA-seq
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