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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doaj-e0dd04f2c0c84f6397ee57a260411be42021-04-02T20:34:43ZengNature Publishing Groupnpj Regenerative Medicine2057-39952021-03-016111510.1038/s41536-021-00120-8The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesionsMariana Di Luca0Emma Fitzpatrick1Denise Burtenshaw2Weimin Liu3Jay-Christian Helt4Roya Hakimjavadi5Eoin Corcoran6Yusof Gusti7Daniel Sheridan8Susan Harman9Catriona Lally10Eileen M. Redmond11Paul A. Cahill12Dublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyUniversity of Rochester, Department of SurgeryUniversity of Rochester, Department of SurgeryDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyTrinity College Dublin, Trinity Centre for Bioengineering, Trinity Biomedical Sciences InstituteUniversity of Rochester, Department of SurgeryDublin City University, Vascular Biology & Therapeutics Group, School of BiotechnologyAbstract 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.https://doi.org/10.1038/s41536-021-00120-8 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 npj Regenerative Medicine |
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 Publishing Group |
series |
npj Regenerative Medicine |
issn |
2057-3995 |
publishDate |
2021-03-01 |
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. |
url |
https://doi.org/10.1038/s41536-021-00120-8 |
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