Defining the nature of human pluripotent stem cell-derived interneurons via single-cell analysis.
Defining the nature of human pluripotent stem cell-derived interneurons via single-cell analysis.
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DOI：
10.1016/j.stemcr.2021.08.006
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发表时间：
2021-10-12
影响因子：
5.9
通讯作者：
Lowry WE
中科院分区：
文献类型：
--
作者：
Allison T;Langerman J;Sabri S;Otero-Garcia M;Lund A;Huang J;Wei X;Samarasinghe RA;Polioudakis D;Mody I;Cobos I;Novitch BG;Geschwind DH;Plath K;Lowry WE
已经描述了小鼠和人脑的抑制性神经元的特化，并且许多研究已经表明多能干细胞（PSC）可以用于在体外产生中间神经元。目前尚不清楚体外方法是否产生人类中间神经元产生大脑中发现的所有亚型，以及体外和体内中间神经元的相似性。我们应用单细胞核和单细胞转录组学来模拟来自人类皮层的中间神经元发育和来自PSC的中间神经元。我们提供了一个直接比较各种体外中间神经元衍生方法，以确定实现的同质性。我们发现PSC衍生的中间神经元捕获妊娠中期之前的发育阶段，并代表了大脑中发现的少数潜在亚型。与在胎儿或成人大脑中发现的那些相比，突出了突触相关基因表达的减少。这些分析强调了定制生成方法以驱动特定亚型形成的潜力。通过各种方法衍生自人多能细胞的中间神经元的比较单细胞分析定义体外衍生的中间神经元的异质性体外和体内衍生的中间神经元的直接比较鉴定发育定义中间神经元的转录模块普拉斯，Lowry及其同事通过各种方法描述了由人类多能干细胞产生的中间神经元，以了解中间神经元培养物的异质性和细胞状态体外使用单细胞分析，作者定义了每种体外方法达到的均匀性和成熟度。通过将这些中间神经元与人脑中出生的中间神经元进行直接比较，作者强调了区别，特别是在突触基因和转录因子模块中，这些基因和转录因子模块区分了体外和体内衍生的神经元。
The specification of inhibitory neurons has been described for the mouse and human brain, and many studies have shown that pluripotent stem cells (PSCs) can be used to create interneurons in vitro. It is unclear whether in vitro methods to produce human interneurons generate all the subtypes found in brain, and how similar in vitro and in vivo interneurons are. We applied single-nuclei and single-cell transcriptomics to model interneuron development from human cortex and interneurons derived from PSCs. We provide a direct comparison of various in vitro interneuron derivation methods to determine the homogeneity achieved. We find that PSC-derived interneurons capture stages of development prior to mid-gestation, and represent a minority of potential subtypes found in brain. Comparison with those found in fetal or adult brain highlighted decreased expression of synapse-related genes. These analyses highlight the potential to tailor the method of generation to drive formation of particular subtypes. Comparison of interneurons derived from human pluripotent cells by various methods Single-cell analyses define heterogeneity of in vitro-derived interneurons Direct comparison of in vitro- and in vivo-derived interneurons Identification of transcriptional modules that developmentally define interneurons Plath, Lowry and colleagues profile interneurons generated from human pluripotent stem cells by various methods to understand the heterogeneity and cellular state of interneuron cultures in vitro. Using single-cell analyses, the authors define the homogeneity and maturity achieved with each in vitro method. By directly comparing these interneurons with those born in the human brain, the authors highlight distinctions particularly in synaptic genes and transcription factor modules that distinguish in vitro- and in vivo-derived neurons.
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影响因子：
3.4
作者：
Gelman, Diego M.;Marin, Oscar
通讯作者：
Marin, Oscar
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
10.5
作者：
Brancho, D;Tanaka, N;Davis, RJ
通讯作者：
Davis, RJ
影响因子：
48
作者：
Habib N;Avraham-Davidi I;Basu A;Burks T;Shekhar K;Hofree M;Choudhury SR;Aguet F;Gelfand E;Ardlie K;Weitz DA;Rozenblatt-Rosen O;Zhang F;Regev A
通讯作者：
Regev A
影响因子：
23.9
作者：
Maroof, Asif M.;Keros, Sotirios;Tyson, Jennifer A.;Ying, Shui-Wang;Ganat, Yosif M.;Merkle, Florian T.;Liu, Becky;Goulburn, Adam;Stanley, Edouard G.;Elefanty, Andrew G.;Widmer, Hans Ruedi;Eggan, Kevin;Goldstein, Peter A.;Anderson, Stewart A.;Studer, Lorenz
通讯作者：
Studer, Lorenz