Jakub Scaber, Iona Thomas-Wright, Alex J Clark, Yinyan Xu, Björn F Vahsen, Mireia Carcolé, Ruxandra Dafinca, Lucy Farrimond, Adrian M Isaacs, David L Bennett, Kevin Talbot
{"title":"iPSC 运动和感觉神经元中 C9ORF72 HRE 导致的细胞和轴突运输表型。","authors":"Jakub Scaber, Iona Thomas-Wright, Alex J Clark, Yinyan Xu, Björn F Vahsen, Mireia Carcolé, Ruxandra Dafinca, Lucy Farrimond, Adrian M Isaacs, David L Bennett, Kevin Talbot","doi":"10.1016/j.stemcr.2024.05.008","DOIUrl":null,"url":null,"abstract":"<p><p>Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"957-972"},"PeriodicalIF":5.9000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252479/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.\",\"authors\":\"Jakub Scaber, Iona Thomas-Wright, Alex J Clark, Yinyan Xu, Björn F Vahsen, Mireia Carcolé, Ruxandra Dafinca, Lucy Farrimond, Adrian M Isaacs, David L Bennett, Kevin Talbot\",\"doi\":\"10.1016/j.stemcr.2024.05.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.</p>\",\"PeriodicalId\":21885,\"journal\":{\"name\":\"Stem Cell Reports\",\"volume\":\" \",\"pages\":\"957-972\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252479/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stemcr.2024.05.008\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.05.008","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
摘要
诱导多能干细胞（iPSC）衍生的运动神经元（MNs）来自肌萎缩性脊髓侧索硬化症（ALS）和C9ORF72六核苷酸重复扩增（HRE）患者，具有多种细胞表型，但其中哪些表型能准确反映ALS细胞特异性脆弱性的生物学基础尚不确定。因此，我们比较了C9ORF72 HRE在MNs和感觉神经元（SNs）中导致的表型，后者在ALS中相对幸免。iPSC 模型能够部分再现成年 SN 和 MN 之间的不同基因表达。我们证明了 C9ORF72-ALS 的典型特征，包括 RNA 病灶和二肽形成，以及特定的轴突运输缺陷，在 MNs 和 SNs 中同样发生，这表明这些体外表型不足以单独解释 ALS 的细胞类型选择性。
Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.
Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.
期刊介绍：
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
