美国哈佛大学Paola Arlotta课题组发现，类器官中细胞类别身份的正确获取定义出人类大脑皮层的命运特化程序。相关论文于2022年9月29日发表在《细胞》杂志上。
研究人员提出了一个全面的单细胞转录组、表观遗传学和人类皮层类器官发育的空间图谱，包括超过61万个细胞，从神经祖细胞的产生到分化的神经元和胶质亚型的产生。结果表明，无论代谢状态如何，细胞多样化的过程与内源性的过程密切相关，从而使研究人员有能力使用这个图谱来研究人类的命运特化。研究人员定义了类器官发育过程中皮层细胞类型的纵向分子轨迹，确定了在谱系建立中具有预测的人类特定作用的基因，并揭示了人类胼胝体神经元的早期转录多样性。这些研究结果验证了这一全面的人类皮层发育体外图谱，是研究人类皮层发育机制的主要资源。
据悉，要实现脑器官研究人类发育的全部效用，需要了解器官是否精确地复制了内源性的细胞和分子事件，特别是由于器官中细胞身份的获得可能会受到异常代谢状态的影响。
附：英文原文
Title: Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex
Author: Ana Uzquiano, Amanda J. Kedaigle, Martina Pigoni, Bruna Paulsen, Xian Adiconis, Kwanho Kim, Tyler Faits, Surya Nagaraja, Noelia Antón-Bolaos, Chiara Gerhardinger, Ashley Tucewicz, Evan Murray, Xin Jin, Jason Buenrostro, Fei Chen, Silvia Velasco, Aviv Regev, Joshua Z. Levin, Paola Arlotta
Issue&Volume: 2022/09/29
Abstract: Realizing the full utility of brain organoids to study human development requiresunderstanding whether organoids precisely replicate endogenous cellular and molecularevents, particularly since acquisition of cell identity in organoids can be impairedby abnormal metabolic states. We present a comprehensive single-cell transcriptomic,epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000cells, from generation of neural progenitors through production of differentiatedneuronal and glial subtypes. We show that processes of cellular diversification correlateclosely to endogenous ones, irrespective of metabolic state, empowering the use ofthis atlas to study human fate specification. We define longitudinal molecular trajectoriesof cortical cell types during organoid development, identify genes with predictedhuman-specific roles in lineage establishment, and uncover early transcriptional diversityof human callosal neurons. The findings validate this comprehensive atlas of humancorticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development.
DOI: 10.1016/j.cell.2022.09.010
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01168-0