Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex.
Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex.
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DOI：
10.1016/j.cell.2022.09.010
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发表时间：
2022-09-29
期刊：
影响因子：
64.5
通讯作者：
Arlotta, Paola
中科院分区：
文献类型：
--
作者：
Uzquiano, Ana;Kedaigle, Amanda J.;Pigoni, Martina;Paulsen, Bruna;Adiconis, Xian;Kim, Kwanho;Faits, Tyler;Nagaraja, Surya;Anton-Bolanos, Noelia;Gerhardinger, Chiara;Tucewicz, Ashley;Murray, Evan;Jin, Xin;Buenrostro, Jason;Chen, Fei;Velasco, Silvia;Regev, Aviv;Levin, Joshua Z.;Arlotta, Paola
要实现脑类器官在研究人类发育方面的全部效用，需要了解类器官是否精确复制内源性细胞和分子事件，特别是因为类器官中细胞身份的获得可能会受到异常代谢状态的损害。我们提出了一个全面的单细胞转录组学，表观遗传学和人类皮质类器官发育的空间图谱，包括超过610，000个细胞，从神经祖细胞的产生到分化的神经元和神经胶质亚型的产生。我们发现，细胞多样化的过程密切相关的内源性的，无论代谢状态，授权使用该图谱来研究人类的命运规范。我们定义了类器官发育过程中皮质细胞类型的纵向分子轨迹，确定了在谱系建立中具有预测人类特异性作用的基因，并揭示了人类胼胝体神经元的早期转录多样性。研究结果验证了这一全面的人类皮质发育的体外图谱作为一种资源，以初步调查人类皮质发育的机制。包括人类皮质类器官发育的单细胞转录组学，表观遗传学和空间图谱的资源表明，类器官中细胞多样化的过程与内源性过程密切相关，无论代谢状态如何，并确定了在谱系建立中具有预测的人类特异性作用的基因。
Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development. A resource encompassing single-cell transcriptomic, epigenetic, and spatial atlases of human cortical organoid development shows that processes of cellular diversification in organoids correlate closely to endogenous ones, irrespective of metabolic state, and identifies genes with predicted human-specific roles in lineage establishment.
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影响因子：
64.8
作者：
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影响因子：
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作者：
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影响因子：
64.8
作者：
Buenrostro JD;Wu B;Litzenburger UM;Ruff D;Gonzales ML;Snyder MP;Chang HY;Greenleaf WJ
通讯作者：
Greenleaf WJ
影响因子：
64.8
作者：
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通讯作者：
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