title: Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion.
abstract: Pref-1 is an EGF-repeat-containing protein that inhibits adipocyte differentiation. To better understand the origin and development of white adipose tissue (WAT), we generated transgenic mouse models for transient or permanent fluorescent labeling of cells using the Pref-1 promoter, facilitating inducible ablation. We show that Pref-1-marked cells retain proliferative capacity and are very early adipose precursors, prior to expression of Zfp423 or PPARγ. In addition, the Pref-1-marked cells establish that adipose precursors are mesenchymal, but not endothelial or pericytal, in origin. During embryogenesis, Pref-1-marked cells first appear in the dorsal mesenteric region as early as embryonic day 10.5 (E10.5). These cells become lipid-laden adipocytes at E17.5 in the subcutaneous region, whereas visceral WAT develops after birth. Finally, ablation of Pref-1-marked cells prevents not only embryonic WAT development but also later adult adipose expansion upon high-fat feeding, demonstrating the requirement of Pref-1 cells for adipogenesis.
authors.affiliation: Department of Nutritional Sciences & Toxicology, 119 Morgan Hall, University of California, Berkeley, CA 94720, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Hudak
authors.affiliation: Endocrinology Program, 299 LSA, University of California, Berkeley, CA 94720, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Gulyaeva
authors.affiliation: Department of Nutritional Sciences & Toxicology, 119 Morgan Hall, University of California, Berkeley, CA 94720, USA.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, 306 Stanley Hall, University of California, Berkeley, CA 94720 USA; Berkeley Sensor and Actuator Center, 403 Cory Hall, University of California, Berkeley, CA 94720, USA; Department of Radiology, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Bioengineering, 306 Stanley Hall, University of California, Berkeley, CA 94720 USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Lee
authors.affiliation: Department of Molecular & Cell Biology, 142 LSA, University of California, Berkeley, CA 94720, USA.
authors.forename: Chulho
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Nutritional Sciences & Toxicology, 119 Morgan Hall, University of California, Berkeley, CA 94720, USA; Endocrinology Program, 299 LSA, University of California, Berkeley, CA 94720, USA. Electronic address: hsul@berkeley.edu.
authors.forename: Hei Sook
authors.initials: HS
authors.lastname: Sul
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C512925:Dlk1 protein, mouse; C484557:Ebfaz protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D014157:Transcription Factors
references.citation: Cell Metab. 2012 Feb 8;15(2):230-9
references.pmid: 22326224
references.citation: Cell Metab. 2009 Mar;9(3):287-302
references.pmid: 19254573
references.citation: Annu Rev Biochem. 2012;81:715-36
references.pmid: 22463691
references.citation: J Clin Invest. 2007 Sep;117(9):2553-61
references.pmid: 17786244
references.citation: Science. 2008 Oct 24;322(5901):583-6
references.pmid: 18801968
references.citation: Front Endocrinol (Lausanne). 2013 Jul 03;4:79
references.pmid: 23840193
references.citation: Genes Dev. 1998 Oct 15;12(20):3168-81
references.pmid: 9784492
references.citation: Bone. 2012 Feb;50(2):477-89
references.pmid: 21872687
references.citation: Stem Cell Rev Rep. 2012 Mar;8(1):55-66
references.pmid: 21365256
references.citation: Mol Cell Biol. 2010 Jul;30(14):3480-92
references.pmid: 20457810
references.citation: Cell Stem Cell. 2011 Jul 8;9(1):1-2
references.pmid: 21683669
references.citation: Nat Cell Biol. 2005 Jun;7(6):543-5
references.pmid: 15928698
references.citation: Biochem Biophys Res Commun. 2013 Jan 18;430(3):871-5
references.pmid: 23268339
references.citation: Cell. 1993 May 21;73(4):725-34
references.pmid: 8500166
references.citation: Mol Cell Biol. 1997 Feb;17(2):977-88
references.pmid: 9001251
references.citation: Cell Metab. 2006 Oct;4(4):263-73
references.pmid: 17011499
references.citation: J Clin Invest. 2003 Feb;111(4):453-61
references.pmid: 12588883
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10482-7
references.pmid: 12145322
references.citation: Nat Commun. 2014 Mar 25;5:3451
references.pmid: 24667995
references.citation: Science. 2004 Jan 16;303(5656):359-63
references.pmid: 14671312
references.citation: Curr Biol. 1998 Mar 26;8(7):377-85
references.pmid: 9545195
references.citation: Physiol Rev. 1998 Jul;78(3):783-809
references.pmid: 9674695
references.citation: Dev Cell. 2011 Jun 14;20(6):815-26
references.pmid: 21664579
references.citation: Nat Cell Biol. 2013 Mar;15(3):302-8
references.pmid: 23434825
references.citation: Cell. 2008 Oct 17;135(2):240-9
references.pmid: 18835024