Mor Grinstein, Stephanie L Tsai, Daniel Montoro, Benjamin R Freedman, Heather L Dingwall, Steffany Villaseñor, Ken Zou, Moshe Sade-Feldman, Miho J Tanaka, David J Mooney, Terence D Capellini, Jayaraj Rajagopal, Jenna L Galloway
{"title":"潜伏的 Axin2+/Scx+ 祖细胞池是肌腱愈合的核心组织者。","authors":"Mor Grinstein, Stephanie L Tsai, Daniel Montoro, Benjamin R Freedman, Heather L Dingwall, Steffany Villaseñor, Ken Zou, Moshe Sade-Feldman, Miho J Tanaka, David J Mooney, Terence D Capellini, Jayaraj Rajagopal, Jenna L Galloway","doi":"10.1038/s41536-024-00370-2","DOIUrl":null,"url":null,"abstract":"<p><p>A tendon's ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx<sup>+</sup>/Axin2<sup>+</sup> population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2<sup>+</sup> cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2<sup>+</sup>-descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2<sup>+</sup> identity. Specific loss of Wnt secretion in Axin2<sup>+</sup> or Scx<sup>+</sup> cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2<sup>+</sup>/Scx<sup>+</sup> cells rely on self-regulation to maintain their identity as key organizers of tissue healing.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487078/pdf/","citationCount":"0","resultStr":"{\"title\":\"A latent Axin2<sup>+</sup>/Scx<sup>+</sup> progenitor pool is the central organizer of tendon healing.\",\"authors\":\"Mor Grinstein, Stephanie L Tsai, Daniel Montoro, Benjamin R Freedman, Heather L Dingwall, Steffany Villaseñor, Ken Zou, Moshe Sade-Feldman, Miho J Tanaka, David J Mooney, Terence D Capellini, Jayaraj Rajagopal, Jenna L Galloway\",\"doi\":\"10.1038/s41536-024-00370-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A tendon's ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx<sup>+</sup>/Axin2<sup>+</sup> population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2<sup>+</sup> cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2<sup>+</sup>-descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2<sup>+</sup> identity. Specific loss of Wnt secretion in Axin2<sup>+</sup> or Scx<sup>+</sup> cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2<sup>+</sup>/Scx<sup>+</sup> cells rely on self-regulation to maintain their identity as key organizers of tissue healing.</p>\",\"PeriodicalId\":54236,\"journal\":{\"name\":\"npj Regenerative Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487078/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Regenerative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41536-024-00370-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Regenerative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41536-024-00370-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
A latent Axin2+/Scx+ progenitor pool is the central organizer of tendon healing.
A tendon's ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx+/Axin2+ population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2+ cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2+-descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2+ identity. Specific loss of Wnt secretion in Axin2+ or Scx+ cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2+/Scx+ cells rely on self-regulation to maintain their identity as key organizers of tissue healing.
期刊介绍：
Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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