The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions

Abstract A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog-responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using...

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Autores principales:	Mariana Di Luca, Emma Fitzpatrick, Denise Burtenshaw, Weimin Liu, Jay-Christian Helt, Roya Hakimjavadi, Eoin Corcoran, Yusof Gusti, Daniel Sheridan, Susan Harman, Catriona Lally, Eileen M. Redmond, Paul A. Cahill
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/e0dd04f2c0c84f6397ee57a260411be4
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spelling	oai:doaj.org-article:e0dd04f2c0c84f6397ee57a260411be42021-12-02T14:40:11ZThe calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions10.1038/s41536-021-00120-82057-3995https://doaj.org/article/e0dd04f2c0c84f6397ee57a260411be42021-03-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00120-8https://doaj.org/toc/2057-3995Abstract A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog-responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100β vSCs in vivo, we identified S100β/Sca1 cells derived from a S100β non-SMC parent population within lesions that co-localise with smooth muscle α-actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100β/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100β and PTCH1 cells were present in human vessels while S100β cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100β neuroectoderm progenitors in vitro. We conclude that hedgehog-responsive S100β vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis.Mariana Di LucaEmma FitzpatrickDenise BurtenshawWeimin LiuJay-Christian HeltRoya HakimjavadiEoin CorcoranYusof GustiDaniel SheridanSusan HarmanCatriona LallyEileen M. RedmondPaul A. CahillNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Mariana Di Luca Emma Fitzpatrick Denise Burtenshaw Weimin Liu Jay-Christian Helt Roya Hakimjavadi Eoin Corcoran Yusof Gusti Daniel Sheridan Susan Harman Catriona Lally Eileen M. Redmond Paul A. Cahill The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
description	Abstract A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog-responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100β vSCs in vivo, we identified S100β/Sca1 cells derived from a S100β non-SMC parent population within lesions that co-localise with smooth muscle α-actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100β/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100β and PTCH1 cells were present in human vessels while S100β cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100β neuroectoderm progenitors in vitro. We conclude that hedgehog-responsive S100β vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis.
format	article
author	Mariana Di Luca Emma Fitzpatrick Denise Burtenshaw Weimin Liu Jay-Christian Helt Roya Hakimjavadi Eoin Corcoran Yusof Gusti Daniel Sheridan Susan Harman Catriona Lally Eileen M. Redmond Paul A. Cahill
author_facet	Mariana Di Luca Emma Fitzpatrick Denise Burtenshaw Weimin Liu Jay-Christian Helt Roya Hakimjavadi Eoin Corcoran Yusof Gusti Daniel Sheridan Susan Harman Catriona Lally Eileen M. Redmond Paul A. Cahill
author_sort	Mariana Di Luca
title	The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
title_short	The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
title_full	The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
title_fullStr	The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
title_full_unstemmed	The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
title_sort	calcium binding protein s100β marks hedgehog-responsive resident vascular stem cells within vascular lesions
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e0dd04f2c0c84f6397ee57a260411be4
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The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions

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