Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA; email:
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Annu Rev Neurosci. 2020 Jul 8;43:375-389. doi: 10.1146/annurev-neuro-070918-050154.
Scientists have been fascinated by the human brain for centuries, yet knowledge of the cellular and molecular events that build the human brain during embryogenesis and of how abnormalities in this process lead to neurological disease remains very superficial. In particular, the lack of experimental models for a process that largely occurs during human in utero development, and is therefore poorly accessible for study, has hindered progress in mechanistic understanding. Advances in stem cell-derived models of human organogenesis, in the form of three-dimensional organoid cultures, and transformative new analytic technologies have opened new experimental pathways for investigation of aspects of development, evolution, and pathology of the human brain. Here, we consider the biology of brain organoids, compared and contrasted with the endogenous human brain, and highlight experimental strategies to use organoids to pioneer new understanding of human brain pathology.
科学家们几个世纪以来一直对人类大脑着迷，但对于在胚胎发生过程中构建人类大脑的细胞和分子事件的了解，以及这一过程中的异常如何导致神经疾病，仍然非常肤浅。特别是，由于这个过程主要发生在人类子宫内发育过程中，因此很难进行研究，缺乏实验模型，阻碍了对其机制的理解。以三维类器官培养为形式的人类器官发生的干细胞衍生模型的进展，以及变革性的新型分析技术，为研究人类大脑的发育、进化和病理学的各个方面开辟了新的实验途径。在这里，我们将比较和对比类器官的生物学特性与内源性人脑，并强调使用类器官开拓人类大脑病理学新认识的实验策略。
