RT Journal Article
T1 Functional vascular smooth muscle-like cells derived from adult mouse uterine mesothelial cells.
A1 Lachaud, Christian Claude
A1 Pezzolla, Daniela
A1 Domínguez-Rodríguez, Alejandro
A1 Smani, Tarik
A1 Soria, Bernat
A1 Hmadcha, Abdelkrim
K1 Immunofluorescence
K1 Muscarinic acetylcholine receptors
K1 Flow cytometry
K1 Carbachol
K1 Fibroblasts
K1 Oxytocin
K1 Fluorescence imaging
K1 Desmin
AB 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.
PB Public Library of Science
YR 2013
FD 2013
LK http://hdl.handle.net/10668/2414
UL http://hdl.handle.net/10668/2414
LA en
NO 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
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 7, 2025