Individual human cortical progenitors can produce excitatory and inhibitory neurons.
Individual human cortical progenitors can produce excitatory and inhibitory neurons.
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DOI：
10.1038/s41586-021-04230-7
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发表时间：
2022-01
期刊：
影响因子：
64.8
通讯作者：
Nowakowski TJ
中科院分区：
文献类型：
--
作者：
Delgado RN;Allen DE;Keefe MG;Mancia Leon WR;Ziffra RS;Crouch EE;Alvarez-Buylla A;Nowakowski TJ
大脑皮层是一种细胞复杂结构，由丰富多样的神经元和神经胶质细胞类型组成。皮质神经元可大致分为两类：谷氨酸能兴奋性神经元和 GABA 能抑制性中间神经元。先前对啮齿类动物的发育研究得出了一种流行的模型，即兴奋性神经元是由位于皮层的祖细胞产生的，而皮层中间神经元是由位于发育中皮层外部神经节隆起的单独的祖细胞群产生的。然而，人类皮质祖细胞的发育潜力尚未得到彻底探索。在这里，我们表明，除了兴奋性神经元和神经胶质细胞外，人类皮质祖细胞还能够产生具有皮质中间神经元转录特征和形态的 GABA 能神经元。通过开发一种名为“用于识别克隆关系的 ScRNAseq 兼容示踪剂”(STICR) 的细胞条形码工具，我们能够对来自 6 个样本的 1912 个原代人类皮质祖细胞进行克隆谱系追踪，并捕获其后代的转录身份和克隆关系。皮质产生的 GABA 能神经元亚群在转录上与尾神经节隆起产生的皮质中间神经元相似，并且这些细胞经常与兴奋性神经元和神经胶质细胞相关。因此，我们的结果表明，个体人类皮质祖细胞可以产生兴奋性神经元和皮质中间神经元，为理解人类皮质神经元多样性的起源提供了一个新的框架。
The cerebral cortex is a cellularly-complex structure comprised of a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Previous developmental studies in rodents have led to the prevailing model that while excitatory neurons are born from progenitors located in the cortex, cortical interneurons are born from a separate population of progenitors located outside of the developing cortex in the ganglionic eminences. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called “ScRNAseq-compatible Tracer for Identifying Clonal Relationships” (STICR), we were able to perform clonal lineage tracing of 1912 primary human cortical progenitors from six specimens and capture both the transcriptional identities and clonal relationships of their resulting progeny. A subpopulation of cortically-born GABAergic neurons were transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence and these cells were frequently related to excitatory neurons and glia. Thus, our results demonstrate that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
3.1
作者：
Alzu'bi A;Lindsay S;Kerwin J;Looi SJ;Khalil F;Clowry GJ
通讯作者：
Clowry GJ
影响因子：
5.7
作者：
Bandler RC;Mayer C;Fishell G
通讯作者：
Fishell G
影响因子：
5.3
作者：
Kohwi, Minoree;Petryniak, Magdalena A.;Alvarez-Buylla, Arturo
通讯作者：
Alvarez-Buylla, Arturo
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