title: Identification and prospective isolation of a mesothelial precursor lineage giving rise to smooth muscle cells and fibroblasts for mammalian internal organs, and their vasculature.
abstract: Fibroblasts and smooth muscle cells (FSMCs) are principal cell types of connective and adventitial tissues that participate in the development, physiology and pathology of internal organs, with incompletely defined cellular origins. Here, we identify and prospectively isolate from the mesothelium a mouse cell lineage that is committed to FSMCs. The mesothelium is an epithelial monolayer covering the vertebrate thoracic and abdominal cavities and internal organs. Time-lapse imaging and transplantation experiments reveal robust generation of FSMCs from the mesothelium. By targeting mesothelin (MSLN), a surface marker expressed on mesothelial cells, we identify and isolate precursors capable of clonally generating FSMCs. Using a genetic lineage tracing approach, we show that embryonic and adult mesothelium represents a common lineage to trunk FSMCs, and trunk vasculature, with minimal contributions from neural crest, or circulating cells. The isolation of FSMC precursors enables the examination of multiple aspects of smooth muscle and fibroblast biology as well as the prospective isolation of these precursors for potential regenerative medicine purposes.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. ryuval@stanford.edu
authors.forename: Yuval
authors.initials: Y
authors.lastname: Rinkevich
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Debashis
authors.initials: D
authors.lastname: Sahoo
authors.forename: Pin-Xian
authors.initials: PX
authors.lastname: Xu
authors.forename: John R
authors.initials: JR
authors.lastname: Bermingham
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D004848:Epithelium / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D007150:Immunohistochemistry; D000090204:Mesothelin; D051379:Mice; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D058851:GPI-Linked Proteins; C000715528:Msln protein, mouse; D013629:Tamoxifen; D000090204:Mesothelin