Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration

Tang, Juan; Wang, Haixiao; Huang, Xiuzhen; Li, Fēi; Zhu, Huan; Li, Yan; He, Lingjuan; Zhang, Hui; Pu, Wenjuan; Li, Kuo; Zhao, Huan; Bentzon, Jacob F.; Yu, Ying; Ji, Yong; Nie, Yu; Tian, Xueying; Zhang, Li; Gao, Dong; Zhou, Bin

doi:10.1016/j.stem.2019.11.010

Cited by 118 publications

(129 citation statements)

References 74 publications

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“…Similarly, undifferentiated stem cells were easily discriminated from their myogenic progeny with the same trained photonic dataset. Using this MLP artificial neural network, we successfully classified sham and ligated cells ex vivo and further predicted the presence of S100β + mVSc and their myogenic progeny within injured vessels confirming our S100β lineage tracing analysis and supporting previous studies that mapped stem cell-derived myogenic progeny to vascular lesions [9,12,13]. Our success in classifying these cells without exogenous contrast agents suggests that modern machine learning approaches may help compensate for spectral data with less molecular specificity and may provide further insight into the function and regulation of stem cells and their progeny in disease.…”

Section: Discussionsupporting

confidence: 83%

“…Despite extensive research, their origin remains controversial 67 . In particular, whether these clonal progeny are derived primarily from differentiated medial SMCs 11,21,66 , endothelial cells 20,68 , and/or resident vascular stem cells (mVSc) 15,20,22,59,69,70 .…”

Section: Discussionmentioning

confidence: 99%

“…In a post-genomic era, information-rich technologies are proving critically important drivers for both fundamental biology and personalised medicine 37 . In particular, scRNA-seq clustering has elucidated cell-to-cell heterogeneity and uncovered cell subgroups and cell dynamics in numerous systems 38 , including vascular 21,22,39 . Label-free technologies for bioanalytical applications have also attracted recent attention with several different classes of label-free sensor detectors now being developed, including plasmonic, photonic, electrical and mechanical sensors 40 .…”

Section: Tgf-β1 Is Released By Both Inflammatory Cells and Vascular Cmentioning

confidence: 99%

“…While some adventitial progenitors are derived from a parent Myh11 + SMC population 17 , non-SMC derived SRY-related HMG-box 10 (Sox10) adventitial/medial resident multipotent vascular stem cells (MVSC) and Nestin + progenitor cells have also been implicated 19,20 . Single cell RNA sequence analysis (scRNA-seq) further suggested that a rare subpopulation of Myh11-Cre marked SMC that are stem cell antigen-1 positive (Sca1 + ) may be entirely responsible 21 while cell fate mapping and scRNA-seq studies also implicated non-SMC adventitial Sca1 + cells as they expand more rapidly than pre-existing SMCs within severe lesions 22 . Despite these insights, the putative role of resident vascular stem cells that do not originate from medial Myh11 + SMCs in promoting intimal thickening remains controversial.…”

Section: Introductionmentioning

confidence: 99%

“…Lineage tracing and single cell RNA sequence analysis (scRNA-seq) have provided compelling evidence in various animal models for the involvement of a population of (i) differentiated myosin heavy chain 11 (Myh11) + medial SMC in progressing intimal thickening [7,8] and (ii) adventitial and medial progenitors in progressing intimal thickening [9][10][11][12]. While some adventitial progenitors are derived from a parent Myh11 + SMC population [10], non-SMC derived SRY-related HMG-box 10 (Sox10) adventitial/medial resident multipotent vascular stem cells (mVSc) [13] and Nestin + progenitor cells have also been implicated [14].…”

Section: Introductionmentioning

confidence: 99%

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Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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Background: A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening, lipid retention and plaque formation, yet their origin remains controversial. The ability to discriminate heterogeneous populations of cells in the context of various disease processes is of potential clinical and diagnostic value. Methods:The feasibility of multivariate analysis of single cell photonics as a discriminator of cell phenotype was assessed using label-free optical multi-parameter interrogation of single cells on a novel Lab-on-a-Disk (LoaD) platform before myogenic differentiation of a series of multipotent stem cells in vitro, and the cellular heterogeneity within vascular lesions in vivo, was determined using supervised machine learning and validated by genetic lineage tracing in vivo.Findings: Single cell photonics were of sufficient coverage, specificity, and quality to discriminate various disparate cell phenotypes in vitro and normal medial SMCs from SMClike cells following injury ex vivo, in addition to distinguishing myogenic differentiation of a series of multipotent stem cells in vitro. Supervised machine learning of these photonic datasets supported genetic lineage tracing analysis and identified the presence of S100β + stem-derived myogenic progeny within vascular lesions, in part, due to upregulation of Coll 3A1 and elastin.Interpretation: Disease-relevant photonic signatures reflect cell type and differentiation state and may have important predictive value as a phenotypic discriminator for vascular disease. Research in contextEvidence before this study: Cardiovascular disease (CVD), the leading cause of death and disability world-wide is characterized by pathological structural changes to the blood vessel wall. Pathologic observations in humans vessels confirm that early 'transitional' lesions enriched with SMC-like cells are routinely present in atherosclerotic-prone regions of arteries during pathologic intimal thickening, prior to lipid retention, and the appearance of a atherosclerotic plaque. Lineage tracing and single cell RNA sequence analysis (scRNA-seq) analysis has provided compelling evidence for the involvement of differentiated medial SMC and adventitial/medial progenitors derived from SMCs in progressing intimal thickening.Despite these insights, the putative role of resident vascular stem cells that do not originate from medial SMCs in promoting intimal thickening remains controversial. Light as a diagnostic and prognostic tool has several advantages including high sensitivity, non-destructive measurement, small or even non-invasive analysis and low limits of detection for early detection of disease phenotypes. In combination with microfluidics, photonics enables real time measurement of single cells in very small sample volumes. To accompany these photonic platforms, deep learning, a subset of supervised machine learning based primarily on artificial neural network geometries, has rapidly grown as a predictive method t...

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Tgf-β1 Is Released By Both Inflammatory Cells and Vascular Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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3D Micro‐Nano Hierarchical Constructs Enabling Transmural Ingrowth of Adventitia Improves the “Fallout endothelialization” of Vascular Grafts

Fu,

Zhang,

Wang

et al. 2024

Adv Funct Materials

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Improving transmural ingrowth of adventitia is believed to promote luminal endothelialization during host remodeling of the vascular graft. However, fabricating vascular grafts with opening microstructures favoring cell ingrowth and tunable mechanical strength warranting clinical safety remains challenging. In this study, an ultrathin nanofibrous lumen stented with a highly porous tube is fabricated to acquire a harmonious balance between mechanical stability and the requisite openness for effective cell recruitment. In vitro examination reveals clinically feasible mechanical bridging of the rabbit carotid artery, such vascular graft with 3D micro‐nano hierarchical structures (3D‐MnHCs) enable fast and sufficient cell ingrowth, including transmural angiogenesis and muscular remodeling by myofibroblasts. Harnessing an integrated spatial transcriptomics approach and angiogenesis inhibition experiments, unprecedented insights revealing the positive roles of vascularized adventitia on “Fallout” endothelialization are provided. To conclude, 3D‐MnHCs offer a“concept of proof” for balancing adequate cell ingrowth and clinically applicable strength and degrading rates, therefore introducing a novel perspective for small caliber arterial regeneration.

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TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques

Zhai,

Lei,

Shi

et al. 2024

Advanced Science

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Atherosclerotic plaque rupture mainly contributes to acute coronary syndrome (ACS). Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in atherosclerotic plaque stability and healing post‐disruption. Here, an expansion of FSP1+ cells in a tandem stenosis (TS) model of atherosclerotic mice is unveiled, predominantly originating from VSMCs through single‐cell RNA sequencing (scRNA‐seq) analyses and VSMC lineage tracing studies. Further investigation identified TEA domain transcription factor 1 (TEAD1) as the key transcription factor driving the trans‐differentiation of VSMCs into fibroblast‐like cells. In vivo experiments using a TS model of plaque rupture demonstrated that TEAD1 played a crucial role in promoting plaque stability and healing post‐rupture through pharmacological or TEAD1‐AAV treatments. Mechanistically, it is found that TEAD1 promoted the expression of fibroblast markers through the Wnt4/β‐Catenin pathway, facilitating the trans‐differentiation. Thus, this study illustrated that TEAD1 played a critical role in promoting the trans‐differentiation of VSMCs into fibroblast‐like cells and subsequent extracellular matrix production through the Wnt4/β‐Catenin pathway. Consequently, this process enhanced the healing mechanisms following plaque rupture, elucidating potential therapeutic avenues for managing atherosclerotic instability.

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Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration

Cited by 118 publications

References 74 publications

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

3D Micro‐Nano Hierarchical Constructs Enabling Transmural Ingrowth of Adventitia Improves the “Fallout endothelialization” of Vascular Grafts

TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques

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