Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.

IF 12.6 1区医学 Q1 IMMUNOLOGY Journal of Experimental Medicine Pub Date : 2023-12-04 Epub Date: 2023-09-20 DOI:10.1084/jem.20230913

Farhad Farjood, Justine D Manos, Yue Wang, Anne L Williams, Cuiping Zhao, Susan Borden, Nazia Alam, Glen Prusky, Sally Temple, Jeffrey H Stern, Nathan C Boles

{"title":"Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.","authors":"Farhad Farjood, Justine D Manos, Yue Wang, Anne L Williams, Cuiping Zhao, Susan Borden, Nazia Alam, Glen Prusky, Sally Temple, Jeffrey H Stern, Nathan C Boles","doi":"10.1084/jem.20230913","DOIUrl":null,"url":null,"abstract":"<p><p>Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"220 12","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510736/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1084/jem.20230913","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

视网膜色素上皮细胞异质性和移植疗效的生物标志物鉴定。

视网膜色素上皮（RPE）细胞的移植对视网膜退行性疾病（如年龄相关性黄斑变性）患者有很大的前景。需要对RPE细胞产品特性和关键质量属性进行深入表征，以提高替代治疗策略的有效性和安全性。在这里，我们使用体细胞和单细胞RNA测序（scRNA-seq）对成人RPE干细胞衍生（RPESC-RPE）细胞产物进行了表征，评估了功能细胞在体外整合为成熟RPE单层的情况，以及通过皇家外科学院大鼠的视觉拯救来评估体内疗效。scRNA-seq在RPESC-RPE产物中揭示了几个不同的亚群，其中一些具有祖细胞标记。我们鉴定了表达与体内功效和细胞整合能力增强相关基因的RPE簇。基因表达分析显示lncRNA（TREX）是体内疗效的预测标志物。TREX敲低降低了RCS大鼠的细胞整合，而过表达增加了体外整合并改善了视觉救援。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.