用诱导多能干细胞模拟威廉姆斯综合症。

Neurogenesis (Austin, Tex.) Pub Date : 2017-02-06 eCollection Date: 2017-01-01 DOI:10.1080/23262133.2017.1283187
Thanathom Chailangkarn, Alysson R Muotri
{"title":"用诱导多能干细胞模拟威廉姆斯综合症。","authors":"Thanathom Chailangkarn, Alysson R Muotri","doi":"10.1080/23262133.2017.1283187","DOIUrl":null,"url":null,"abstract":"<p><p>The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model. Using the cellular reprogramming approach, we reported that WS iPSC-derived neural progenitor cells (NPCs) has increased apoptosis and therefore increased doubling time, which could be rescued by complementation of frizzled 9, one of the genes typically deleted in WS. Moreover, WS iPSC-derived CTIP2-positive pyramidal neurons exhibit morphologic alterations including longer total dendrites and increasing dendritic spine number. In addition, WS iPSC-derived neurons show an increase in calcium transient frequency and synchronized activity likely due to increased number of dendritic spines and synapses. Our work integrated cross-level data from genetics to behavior of WS individuals and revealed altered cellular phenotypes in WS human NPCs and neurons that could be validated in other model systems such as magnetic resonance imaging (MRI) in live subjects and postmortem brain tissues.</p>","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":"4 1","pages":"e1283187"},"PeriodicalIF":0.0000,"publicationDate":"2017-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305168/pdf/kngs-04-01-1283187.pdf","citationCount":"0","resultStr":"{\"title\":\"Modeling Williams syndrome with induced pluripotent stem cells.\",\"authors\":\"Thanathom Chailangkarn, Alysson R Muotri\",\"doi\":\"10.1080/23262133.2017.1283187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model. Using the cellular reprogramming approach, we reported that WS iPSC-derived neural progenitor cells (NPCs) has increased apoptosis and therefore increased doubling time, which could be rescued by complementation of frizzled 9, one of the genes typically deleted in WS. Moreover, WS iPSC-derived CTIP2-positive pyramidal neurons exhibit morphologic alterations including longer total dendrites and increasing dendritic spine number. In addition, WS iPSC-derived neurons show an increase in calcium transient frequency and synchronized activity likely due to increased number of dendritic spines and synapses. Our work integrated cross-level data from genetics to behavior of WS individuals and revealed altered cellular phenotypes in WS human NPCs and neurons that could be validated in other model systems such as magnetic resonance imaging (MRI) in live subjects and postmortem brain tissues.</p>\",\"PeriodicalId\":74274,\"journal\":{\"name\":\"Neurogenesis (Austin, Tex.)\",\"volume\":\"4 1\",\"pages\":\"e1283187\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-02-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305168/pdf/kngs-04-01-1283187.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurogenesis (Austin, Tex.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/23262133.2017.1283187\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurogenesis (Austin, Tex.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/23262133.2017.1283187","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

诱导多能干细胞(iPSCs)的发展为研究相关细胞类型的疾病提供了前所未有的新机会。在我们最近的研究中,威廉姆斯综合征(WS)是一种罕见的遗传性神经发育障碍,由 7 号染色体上 25-28 个基因的半杂合性缺失引起。由于缺乏相关的人类细胞模型,人们对这些缺失基因对神经水平的分子和细胞表型的影响知之甚少。我们利用细胞重编程方法报道了 WS iPSC 衍生的神经祖细胞(NPCs)凋亡增加,因此倍增时间延长,而 WS 中典型的缺失基因之一 frizzled 9 的互补可以挽救这种情况。此外,WS iPSC 衍生的 CTIP2 阳性锥体神经元表现出形态学改变,包括总树突变长和树突棘数量增加。此外,WS iPSC 衍生的神经元显示出钙瞬态频率和同步活动的增加,这可能是由于树突棘和突触数量的增加。我们的工作整合了从遗传学到 WS 患者行为的跨层次数据,揭示了 WS 人类 NPCs 和神经元中改变的细胞表型,这些表型可在其他模型系统中得到验证,如活体磁共振成像(MRI)和死后脑组织。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Modeling Williams syndrome with induced pluripotent stem cells.

The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model. Using the cellular reprogramming approach, we reported that WS iPSC-derived neural progenitor cells (NPCs) has increased apoptosis and therefore increased doubling time, which could be rescued by complementation of frizzled 9, one of the genes typically deleted in WS. Moreover, WS iPSC-derived CTIP2-positive pyramidal neurons exhibit morphologic alterations including longer total dendrites and increasing dendritic spine number. In addition, WS iPSC-derived neurons show an increase in calcium transient frequency and synchronized activity likely due to increased number of dendritic spines and synapses. Our work integrated cross-level data from genetics to behavior of WS individuals and revealed altered cellular phenotypes in WS human NPCs and neurons that could be validated in other model systems such as magnetic resonance imaging (MRI) in live subjects and postmortem brain tissues.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Role of neoblasts in the patterned postembryonic growth of the platyhelminth Macrostomum lignano. There's no place like home - HGF-c-MET signaling and melanocyte migration into the mammalian cochlea Effects of Isx-9 and stress on adult hippocampal neurogenesis: Experimental considerations and future perspectives. Opportunities lost and gained: Changes in progenitor competence during nervous system development. Endogenous Brain Repair: Overriding intrinsic lineage determinates through injury-induced micro-environmental signals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1