Publication:
Functional vascular smooth muscle-like cells derived from adult mouse uterine mesothelial cells.

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Abstract
In mammalian visceral organs, vascular smooth muscle cells (VSMCs) originate from an epithelial-to-mesenchymal transition (EMT) of embryonic mesothelial cells (MCs). The ability of adult MCs to recapitulate EMT and to acquire smooth muscle (SM) markers upon provasculogenic culture suggested they might retain embryonic vasculogenic differentiation potential. However, it remains unknown whether adult MCs-derived SM-like cells may acquire specific vascular SM lineage markers and the functionality of differentiated contractile VSMCs. Here, we describe how a gentle trypsinization of adult mouse uterine cords could selectively detach their outermost uterine mesothelial layer cells. As other MCs; uterine MCs (UtMCs) uniformly expressed the epithelial markers β-catenin, ZO-1, E-cadherin, CD54, CD29, and CK18. When cultured in a modified SM differentiation media (SMDM) UtMCs initiated a loss of epithelial characteristics and gained markers expression of EMT (Twist, Snail, and Slug), stem and progenitor (Nanog, Sox2, C-kit, Gata-4, Isl-1, and nestin), SM (α-SMA, calponin, caldesmon, SM22α, desmin, SM-MHC, and smoothelin-B) and cardiac (BMP2, BMP4, ACTC1, sACTN, cTnI, cTnT, ANF, Cx43, and MLC2a). UtMCs repeatedly subcultured in SMDM acquired differentiated VSM-like characteristics and expressed smoothelin-B in the typical stress-fiber pattern expression of contractile VSMCs. Relevantly, UtMCs-derived VSM-like cells could generate "mechanical force" to compact collagen lattices and displayed in diverse degree voltage (K(+)) and receptor (endothelin-1, oxytocin, norepinephrine, carbachol and vasopressin)-induced [Ca(2+)](i) rises and contraction. Thus, we show for the first time that UtMCs could recapitulate in vitro differentiative events of early cardiovascular differentiation and transdifferentiate in cells exhibiting molecular and functional characteristics of VSMCs.
Description
Journal Article; Research Support, Non-U.S. Gov't;
MeSH Terms
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Antigens, Differentiation::Antigens, CD29
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Cell Adhesion Molecules::Cadherins
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Calcium
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal Transition
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Antigens, Differentiation::Antigens, CD::Intercellular Adhesion Molecule-1
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Muscle Contraction
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Contractile Proteins::Muscle Proteins
Medical Subject Headings::Anatomy::Tissues::Muscles::Muscle, Smooth::Muscle, Smooth, Vascular
Medical Subject Headings::Anatomy::Cells::Muscle Cells::Myocytes, Smooth Muscle
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Endothelin
Medical Subject Headings::Anatomy::Urogenital System::Genitalia::Genitalia, Female::Uterus
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::beta Catenin
Medical Subject Headings::Organisms::Eukaryota::Animals
DeCS Terms
CIE Terms
Keywords
Immunofluorescence, Muscarinic acetylcholine receptors, Flow cytometry, Carbachol, Fibroblasts, Oxytocin, Fluorescence imaging, Desmin
Citation
Lachaud CC, Pezzolla D, Domínguez-Rodríguez A, Smani T, Soria B, Hmadcha A. Functional vascular smooth muscle-like cells derived from adult mouse uterine mesothelial cells. PLoS ONE; 8(2):e55181