title: Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion.
abstract: Despite the growing interest in adipose tissue as a therapeutic target of metabolic diseases, the identity of adipocyte precursor cells (preadipocytes) and the formation of adipose tissue during embryonic development are still poorly understood. Here, we clarified the identity and dynamic processes of preadipocytes in mouse white adipose tissue during embryogenesis through direct examination, lineage tracing and culture systems. Surprisingly, we found that lipid-lacking but perilipin(+) or adiponectin(+) proliferating preadipocytes started to emerge at embryonic day 16.5, and these cells underwent active proliferation until birth. Moreover, these preadipocytes resided as clusters and were distributed along growing adipose vasculatures. Importantly, the embryonic preadipocytes exhibited considerable coexpression of stem cell markers, such as CD24, CD29 and PDGFRα, and a small portion of preadipocytes were derived from PDGFRβ(+) mural cells, in contrast to the adult preadipocytes present in the stromal vascular fraction. Further analyses with in vitro and ex vivo culture systems revealed a stepwise but dynamic regulation of preadipocyte formation and differentiation during prenatal adipogenesis. To conclude, we unraveled the identity and characteristics of embryonic preadipocytes, which are crucial for the formation and expansion of adipose tissue during embryogenesis.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Ki Yong
authors.initials: KY
authors.lastname: Hong
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Hosung
authors.initials: H
authors.lastname: Bae
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Intae
authors.initials: I
authors.lastname: Park
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Park
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Kyun Hoo
authors.initials: KH
authors.lastname: Kim
authors.affiliation: The Laboratory of Vascular Biology, Keio University, Tokyo 160-8582, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Laboratory for Craniofacial Biology, Cluster for Craniofacial Development and Regeneration Research, Chonbuk National University School of Dentistry, Jeonju 561-756, Korea.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Hail
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Faculty of Medicine, University of Münster, 48149 Münster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea gykoh@kaist.ac.kr ojyoo@kaist.ac.kr.
authors.forename: Ook-Joon
authors.initials: OJ
authors.lastname: Yoo
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea gykoh@kaist.ac.kr ojyoo@kaist.ac.kr.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000098:blood supply / Q000196:embryology*; D000818:Animals; D001391:Azo Compounds; D051927:CD24 Antigen / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D005697:Galactosides; D007211:Indoles; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D001391:Azo Compounds; D051927:CD24 Antigen; D002352:Carrier Proteins; C497890:Cd24a protein, mouse; D005697:Galactosides; D007211:Indoles; D019012:Integrin beta1; D000070778:Perilipin-1; D010750:Phosphoproteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; C011049:oil red O; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
keywords: Adipogenesis; Adipose tissue; Angiogenesis; Preadipocytes