To reveal the trajectories of smooth muscle cell (SMC) transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, researchers combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques.
[Circulation]
1254621 {1254621:Q2ZDY6S3} apa 50 1 154431 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-e5c2eb61c19722f2d4c180c6f49d4478%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22Q2ZDY6S3%22%2C%22library%22%3A%7B%22id%22%3A1254621%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Pan%20Huize%20et%20al.%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EPan%20Huize%2C%20Xue%20Chenyi%2C%20Auerbach%20Benjamin%20J.%2C%20Fan%20Jiaxin%2C%20Bashore%20Alexander%20C.%2C%20Cui%20Jian%2C%20Yang%20Dina%20Y.%2C%20Trignano%20Sarah%20B.%2C%20Liu%20Wen%2C%20Shi%20Jianting%2C%20Ihuegbu%20Chinyere%20O.%2C%20Bush%20Erin%20C.%2C%20Worley%20Jeremy%2C%20Vlahos%20Lukas%2C%20Laise%20Pasquale%2C%20Solomon%20Robert%20A.%2C%20Connolly%20Edward%20S.%2C%20Califano%20Andrea%2C%20Sims%20Peter%20A.%2C%20%26%23x2026%3B%20Reilly%20Muredach%20P.%20%28n.d.%29.%20Single-Cell%20Genomics%20Reveals%20a%20Novel%20Cell%20State%20During%20Smooth%20Muscle%20Cell%20Phenotypic%20Switching%20and%20Potential%20Therapeutic%20Targets%20for%20Atherosclerosis%20in%20Mouse%20and%20Human.%20%3Ci%3ECirculation%3C%5C%2Fi%3E%2C%20%3Ci%3E0%3C%5C%2Fi%3E%280%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCULATIONAHA.120.048378%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCULATIONAHA.120.048378%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D1254621%26amp%3Bitem_key%3DQ2ZDY6S3%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Single-Cell%20Genomics%20Reveals%20a%20Novel%20Cell%20State%20During%20Smooth%20Muscle%20Cell%20Phenotypic%20Switching%20and%20Potential%20Therapeutic%20Targets%20for%20Atherosclerosis%20in%20Mouse%20and%20Human%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Pan%20Huize%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Xue%20Chenyi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Auerbach%20Benjamin%20J.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Fan%20Jiaxin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Bashore%20Alexander%20C.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Cui%20Jian%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Yang%20Dina%20Y.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Trignano%20Sarah%20B.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Liu%20Wen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Shi%20Jianting%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Ihuegbu%20Chinyere%20O.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Bush%20Erin%20C.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Worley%20Jeremy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Vlahos%20Lukas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Laise%20Pasquale%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Solomon%20Robert%20A.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Connolly%20Edward%20S.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Califano%20Andrea%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Sims%20Peter%20A.%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Zhang%20Hanrui%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Li%20Mingyao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Reilly%20Muredach%20P.%22%7D%5D%2C%22abstractNote%22%3A%22Background%3A%20Smooth%20muscle%20cells%20%28SMC%29%20play%20significant%20roles%20in%20atherosclerosis%20via%20phenotypic%20switching%2C%20a%20pathological%20process%20in%20which%20SMC%20dedifferentiation%2C%20migration%20and%20transdifferentiation%20into%20other%20cell%20types.%20Yet%2C%20how%20SMC%20contribute%20to%20pathophysiology%20of%20atherosclerosis%20remains%20elusive.%20%5CnMethods%3A%20To%20reveal%20the%20trajectories%20of%20SMC%20transdifferentiation%20during%20atherosclerosis%20and%20to%20identify%20molecular%20targets%20for%20disease%20therapy%2C%20we%20combined%20SMC%20fate%20mapping%20and%20single-cell%20RNA%20sequencing%20of%20both%20mouse%20and%20human%20atherosclerotic%20plaques.%20We%20also%20performed%20cell%20biology%20experiments%20on%20isolated%20SMC-derived%20cells%2C%20conducted%20integrative%20human%20genomics%2C%20and%20employed%20pharmacological%20studies%20targeting%20SMC-derived%20cells%20both%20in%20vivo%20and%20in%20vitro.%20%5CnResults%3A%20We%20found%20that%20SMC%20transitioned%20to%20an%20intermediate%20cell%20state%20during%20atherosclerosis%2C%20which%20was%20also%20found%20in%20human%20atherosclerotic%20plaques%20of%20carotid%20and%20coronary%20arteries.%20SMC-derived%20intermediate%20cells%2C%20termed%20%5C%22SEM%5C%22%20cells%2C%20were%20multipotent%20and%20could%20differentiate%20into%20macrophage-like%20and%20fibrochondrocyte-like%20cells%2C%20as%20well%20as%20return%20towards%20SMC%20phenotype.%20Retinoic%20acid%20%28RA%29%20signaling%20was%20identified%20as%20a%20regulator%20of%20SMC%20to%20SEM%20cell%20transition%20and%20RA%20signaling%20was%20dysregulated%20in%20symptomatic%20human%20atherosclerosis.%20Human%20genomics%20revealed%20enrichment%20of%20genome%20wide%20association%20study%20%28GWAS%29%20signals%20for%20coronary%20artery%20disease%20%28CAD%29%20in%20RA%20signaling%20target%20gene%20loci%20and%20correlation%20between%20CAD%20risk%20alleles%20and%20repressed%20expression%20of%20these%20genes.%20Activation%20of%20RA%20signaling%20by%20all-trans%20retinoic%20acid%20%28ATRA%29%2C%20an%20anti-cancer%20drug%20for%20acute%20promyelocytic%20leukemia%2C%20blocked%20SMC%20transition%20to%20SEM%20cells%2C%20reduced%20atherosclerotic%20burden%20and%20promoted%20fibrous%20cap%20stability.%5CnConclusions%3A%20Integration%20of%20cell-specific%20fate%20mapping%2C%20single-cell%20genomics%20and%20human%20genetics%20adds%20novel%20insights%20into%20the%20complexity%20of%20SMC%20biology%20and%20reveals%20regulatory%20pathways%20for%20therapeutic%20targeting%20of%20SMC%20transitions%20in%20atherosclerotic%20cardiovascular%20disease.%22%2C%22date%22%3A%22%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1161%5C%2FCIRCULATIONAHA.120.048378%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.ahajournals.org%5C%2Fdoi%5C%2F10.1161%5C%2FCIRCULATIONAHA.120.048378%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222020-09-23T17%3A29%3A50Z%22%7D%7D%5D%7D
Pan Huize, Xue Chenyi, Auerbach Benjamin J., Fan Jiaxin, Bashore Alexander C., Cui Jian, Yang Dina Y., Trignano Sarah B., Liu Wen, Shi Jianting, Ihuegbu Chinyere O., Bush Erin C., Worley Jeremy, Vlahos Lukas, Laise Pasquale, Solomon Robert A., Connolly Edward S., Califano Andrea, Sims Peter A., … Reilly Muredach P. (n.d.). Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human. Circulation, 0(0). https://doi.org/10.1161/CIRCULATIONAHA.120.048378 Cite