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      Origin and differentiation of vascular smooth muscle cells

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          Abstract

          Vascular smooth muscle cells (SMCs), a major structural component of the vessel wall, not only play a key role in maintaining vascular structure but also perform various functions. During embryogenesis, SMC recruitment from their progenitors is an important step in the formation of the embryonic vascular system. SMCs in the arterial wall are mostly quiescent but can display a contractile phenotype in adults. Under pathophysiological conditions, i.e. vascular remodelling after endothelial dysfunction or damage, contractile SMCs found in the media switch to a secretory type, which will facilitate their ability to migrate to the intima and proliferate to contribute to neointimal lesions. However, recent evidence suggests that the mobilization and recruitment of abundant stem/progenitor cells present in the vessel wall are largely responsible for SMC accumulation in the intima during vascular remodelling such as neointimal hyperplasia and arteriosclerosis. Therefore, understanding the regulatory mechanisms that control SMC differentiation from vascular progenitors is essential for exploring therapeutic targets for potential clinical applications. In this article, we review the origin and differentiation of SMCs from stem/progenitor cells during cardiovascular development and in the adult, highlighting the environmental cues and signalling pathways that control phenotypic modulation within the vasculature.

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          Most cited references141

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          Molecular regulation of vessel maturation.

          The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature--a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.
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            miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

            SUMMARY microRNAs are regulators of myriad cellular events, but evidence for a single microRNA that can efficiently differentiate multipotent cells into a specific lineage or regulate direct reprogramming of cells into an alternate cell fate has been elusive. Here, we show that miR-145 and miR-143 are co-transcribed in multipotent cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem cell–derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2.5, and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4, myocardin, and Elk-1 to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.
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              Hematopoietic stem cells derive directly from aortic endothelium during development

              A major goal of regenerative medicine is to instruct formation of multipotent, tissue-specific stem cells from induced pluripotent stem cells (iPSCs) for cell replacement therapies. Generation of hematopoietic stem cells (HSCs) from iPSCs or embryonic stem cells (ESCs) is not currently possible, however, necessitating a better understanding of how HSCs normally arise during embryonic development. We previously showed that hematopoiesis occurs through four distinct waves during zebrafish development, with HSCs arising in the final wave in close association with the dorsal aorta. Recent reports have suggested that murine HSCs derive from hemogenic endothelial cells (ECs) lining the aortic floor1,2. Additional in vitro studies have similarly suggested that the hematopoietic progeny of ESCs arise through intermediates with endothelial potential3,4. In this report, we have utilized the unique strengths of the zebrafish embryo to image directly the birth of HSCs from the ventral wall of the dorsal aorta. Utilizing combinations of fluorescent reporter transgenes, confocal timelapse microscopy and flow cytometry, we have identified and isolated the stepwise intermediates as aortic hemogenic endothelium transitions to nascent HSCs. Finally, using a permanent lineage tracing strategy, we demonstrate that the HSCs generated from hemogenic endothelium are the lineal founders of the adult hematopoietic system.
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                Author and article information

                Journal
                J Physiol
                J. Physiol. (Lond.)
                10.1111/(ISSN)1469-7793
                TJP
                jphysiol
                The Journal of Physiology
                John Wiley and Sons Inc. (Hoboken )
                0022-3751
                1469-7793
                15 July 2015
                09 June 2015
                : 593
                : 14 ( doiID: 10.1113/jphysiol.2015.593.issue-14 )
                : 3013-3030
                Affiliations
                [ 1 ] Department of Emergency Medicine, the Second Affiliated HospitalXi'an Jiaotong University Xi'anChina
                [ 2 ] Cardiovascular DivisionKing's College London BHF Centre LondonUK
                Author notes
                [*] [* ] Corresponding author Q. Xu: Cardiovascular Division, King's College London BHF Centre, 125 Coldharbour Lane, London SE5 9NU, UK. Email: qingbo.xu@ 123456kcl.ac.uk
                Article
                TJP6687
                10.1113/JP270033
                4532522
                25952975
                50fcaf0c-b60d-4111-9302-abd37d21b0da
                © 2015 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 December 2014
                : 19 April 2015
                Page count
                Pages: 18
                Funding
                Funded by: British Heart Foundation
                Award ID: RG/14/6/31144
                Funded by: Oak Foundation
                Categories
                Topical Review
                Cardiovascular
                Topical Review
                Topical Reviews
                Custom metadata
                2.0
                tjp6687
                15 July 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.1 mode:remove_FC converted:23.06.2016

                Human biology
                Human biology

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