Your browser doesn't support javascript.
loading
Single-Molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-Related CARTPT-Expressing Smooth Muscle Cells.
Mizrak, Dogukan; Zhao, Yang; Feng, Hao; Macaulay, Jane; Tang, Ying; Sultan, Zain; Zhao, Guizhen; Guo, Yanhong; Zhang, Jifeng; Yang, Bo; Chen, Y Eugene.
Afiliação
  • Mizrak D; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Zhao Y; Department of Internal Medicine (Y.Z., G.Z., Y.G., J.Z., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Feng H; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Macaulay J; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Tang Y; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Sultan Z; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Zhao G; Department of Internal Medicine (Y.Z., G.Z., Y.G., J.Z., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Guo Y; Department of Internal Medicine (Y.Z., G.Z., Y.G., J.Z., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Zhang J; Department of Internal Medicine (Y.Z., G.Z., Y.G., J.Z., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Yang B; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
  • Chen YE; Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
Arterioscler Thromb Vasc Biol ; 43(12): 2285-2297, 2023 12.
Article em En | MEDLINE | ID: mdl-37823268
BACKGROUND: Although single-cell RNA-sequencing is commonly applied to dissect the heterogeneity in human tissues, it involves the preparation of single-cell suspensions via cell dissociation, causing loss of spatial information. In this study, we employed high-resolution single-cell transcriptome imaging to reveal rare smooth muscle cell (SMC) types in human thoracic aortic aneurysm (TAA) tissue samples. METHODS: Single-molecule spatial distribution of transcripts from 140 genes was analyzed in fresh-frozen human TAA samples with region and sex-matched controls. In vitro studies and tissue staining were performed to examine human CART prepropeptide (CARTPT) regulation and function. RESULTS: We captured thousands of cells per sample including a spatially distinct CARTPT-expressing SMC subtype enriched in male TAA samples. Immunoassays confirmed human CART (cocaine- and amphetamine-regulated transcript) protein enrichment in male TAA tissue and truncated CARTPT secretion into cell culture medium. Oxidized low-density lipoprotein, a cardiovascular risk factor, induced CARTPT expression, whereas CARTPT overexpression in human aortic SMCs increased the expression of key osteochondrogenic transcription factors and reduced contractile gene expression. Recombinant human CART treatment of human SMCs further confirmed this phenotype. Alizarin red staining revealed calcium deposition in male TAA samples showing similar localization with human CART staining. CONCLUSIONS: Here, we demonstrate the feasibility of single-molecule imaging in uncovering rare SMC subtypes in the diseased human aorta, a difficult tissue to dissociate. We identified a spatially distinct CARTPT-expressing SMC subtype enriched in male human TAA samples. Our functional studies suggest that human CART promotes osteochondrogenic switch of aortic SMCs, potentially leading to medial calcification of the thoracic aorta.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Calcinose / Aneurisma da Aorta Torácica Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Arterioscler Thromb Vasc Biol Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Calcinose / Aneurisma da Aorta Torácica Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Arterioscler Thromb Vasc Biol Ano de publicação: 2023 Tipo de documento: Article