Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells.
Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells.
复制标题
DOI：
10.1016/j.isci.2023.106995
复制
发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Barrett, Lindy E.
中科院分区：
文献类型：
--
作者：
Berryer, Martin H.;Tegtmeyer, Matthew;Binan, Loic;Valakh, Vera;Nathanson, Anna;Trendafilova, Darina;Crouse, Ethan;Klein, Jenny A.;Meyer, Daniel;Pietilainen, Olli;Rapino, Francesca;Farhi, Samouil L.;Rubin, Lee L.;Mccarroll, Steven A.;Nehme, Ralda;Barrett, Lindy E.
新出现的证据表明，星形胶质细胞的物种差异特征与人脑组织的相对不可接近性相结合，强调了人类多能干细胞（hPSC）技术用于人类星形胶质细胞的产生和研究的实用性。然而，用于hPSC-星形胶质细胞生成的现有方法通常是冗长的或需要中间纯化步骤。在这里，我们建立了一个快速和高度可扩展的方法，用于产生功能性的人诱导星形胶质细胞（hiAs）。这些hiAs表达典型的星形胶质细胞标志物，对促炎刺激作出反应，表现出ATP诱导的钙瞬变，并支持神经元网络发育。此外，单细胞转录组学分析揭示了在个体供体中产生高度可重复的细胞群，主要类似于人胎儿星形胶质细胞。最后，从21三体疾病模型产生的hiAs鉴定了细胞-细胞粘附和突触信号传导的预期改变，支持其用于疾病建模应用的效用。因此，hiAs为研究疾病中基本的人类星形胶质细胞功能和功能障碍提供了有价值的和实用的资源。使用瞬时NGN 2和星形胶质细胞培养基从iPSC快速生成人星形胶质细胞评估炎症反应、钙动力学和神经元网络支持在单细胞水平和跨独立细胞系的高度同质性21三体疾病模型中概括的星形胶质细胞功能障碍的关键特征神经科学;转录组学;生物科学方法
Emerging evidence of species divergent features of astrocytes coupled with the relative inaccessibility of human brain tissue underscore the utility of human pluripotent stem cell (hPSC) technologies for the generation and study of human astrocytes. However, existing approaches for hPSC-astrocyte generation are typically lengthy or require intermediate purification steps. Here, we establish a rapid and highly scalable method for generating functional human induced astrocytes (hiAs). These hiAs express canonical astrocyte markers, respond to pro-inflammatory stimuli, exhibit ATP-induced calcium transients and support neuronal network development. Moreover, single-cell transcriptomic analyses reveal the generation of highly reproducible cell populations across individual donors, mostly resembling human fetal astrocytes. Finally, hiAs generated from a trisomy 21 disease model identify expected alterations in cell-cell adhesion and synaptic signaling, supporting their utility for disease modeling applications. Thus, hiAs provide a valuable and practical resource for the study of basic human astrocyte function and dysfunction in disease. Rapid human astrocyte generation from iPSCs using transient NGN2 and astrocyte media Assessment of inflammatory response, calcium dynamics and neuronal network support High homogeneity at the single cell level and across independent cell lines Key features of astrocyte dysfunction recapitulated in a trisomy 21 disease model Neuroscience; Transcriptomics; Methodology in biological sciences
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1111/j.1749-6632.1988.tb51417.x
发表时间：
1988-01-01
影响因子：
5.2
作者：
Goldstein, G W
通讯作者：
Goldstein, G W
影响因子：
64.8
作者：
Bhaduri A;Sandoval-Espinosa C;Otero-Garcia M;Oh I;Yin R;Eze UC;Nowakowski TJ;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
23.9
作者：
Han, Xiaoning;Chen, Michael;Wang, Fushun;Windrem, Martha;Wang, Su;Shanz, Steven;Xu, Qiwu;Oberheim, Nancy Ann;Bekar, Lane;Betstadt, Sarah;Silva, Alcino J.;Takano, Takahiro;Goldman, Steven A.;Nedergaard, Maiken
通讯作者：
Nedergaard, Maiken
影响因子：
11
作者：
Allen, Megan;Huang, Ben S.;Notaras, Michael J.;Lodhi, Aiman;Barrio-Alonso, Estibaliz;Lituma, Pablo J.;Wolujewicz, Paul;Witztum, Jonathan;Longo, Francesco;Chen, Maoshan;Greening, David W.;Klann, Eric;Ross, M. Elizabeth;Liston, Conor;Colak, Dilek
通讯作者：
Colak, Dilek