دورية أكاديمية
Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis.
| العنوان: | Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. |
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| المؤلفون: | Wirka RC; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Wagh D; Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA, USA., Paik DT; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Pjanic M; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Nguyen T; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Miller CL; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA., Kundu R; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Nagao M; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Coller J; Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA, USA., Koyano TK; Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA., Fong R; Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA., Woo YJ; Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA., Liu B; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Montgomery SB; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Wu JC; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Zhu K; Department of Neurology, University of Arizona, Tucson, AZ, USA.; Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA., Chang R; Department of Neurology, University of Arizona, Tucson, AZ, USA.; Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA., Alamprese M; Department of Neurology, University of Arizona, Tucson, AZ, USA.; Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA., Tallquist MD; Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA., Kim JB; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford, CA, USA., Quertermous T; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA. tomq1@stanford.edu.; Stanford Cardiovascular Institute, Stanford, CA, USA. tomq1@stanford.edu. |
| المصدر: | Nature medicine [Nat Med] 2019 Aug; Vol. 25 (8), pp. 1280-1289. Date of Electronic Publication: 2019 Jul 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
| مواضيع طبية MeSH: | Basic Helix-Loop-Helix Transcription Factors/*genetics , Coronary Artery Disease/*prevention & control , Myocytes, Smooth Muscle/*physiology , Single-Cell Analysis/*methods, Animals ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Cells, Cultured ; Humans ; Mice ; Mice, Inbred C57BL ; Osteoprotegerin/genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Sequence Analysis, RNA |
| مستخلص: | In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed 'fibromyocytes', rather than into a classical macrophage phenotype. SMC-specific knockout of TCF21-a causal CAD gene-markedly inhibited SMC phenotypic modulation in mice, leading to the presence of fewer fibromyocytes within lesions as well as within the protective fibrous cap of the lesions. Moreover, TCF21 expression was strongly associated with SMC phenotypic modulation in diseased human coronary arteries, and higher levels of TCF21 expression were associated with decreased CAD risk in human CAD-relevant tissues. These results establish a protective role for both TCF21 and SMC phenotypic modulation in this disease. |
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| معلومات مُعتمدة: | R01 HL109512 United States HL NHLBI NIH HHS; R01 HL144067 United States HL NHLBI NIH HHS; R01 DK107437 United States DK NIDDK NIH HHS; R01 HL139478 United States HL NHLBI NIH HHS; K08 HL133375 United States HL NHLBI NIH HHS; R01 HL103635 United States HL NHLBI NIH HHS; S10 OD018220 United States OD NIH HHS; S10 RR025518 United States RR NCRR NIH HHS; R33 HL120757 United States HL NHLBI NIH HHS; R21 HL120757 United States HL NHLBI NIH HHS; F32 HL129670 United States HL NHLBI NIH HHS; R01 HL148239 United States HL NHLBI NIH HHS; R01 HL134817 United States HL NHLBI NIH HHS; R01 HL141371 United States HL NHLBI NIH HHS; R00 HL125912 United States HL NHLBI NIH HHS; R01 HL145708 United States HL NHLBI NIH HHS; P30 DK116074 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Transcription Factors) 0 (Osteoprotegerin) 0 (TCF21 protein, human) 0 (TNFRSF11B protein, human) |
| تواريخ الأحداث: | Date Created: 20190731 Date Completed: 20191106 Latest Revision: 20220420 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7274198 |
| DOI: | 10.1038/s41591-019-0512-5 |
| PMID: | 31359001 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-170X |
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| DOI: | 10.1038/s41591-019-0512-5 |