Uncovering cell biology in the third dimension.
Uncovering cell biology in the third dimension.
复制标题
揭示三维细胞生物学。
DOI：
10.1091/mbc.e19-04-0211
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发表时间：
2020
影响因子：
3.3
通讯作者：
Gama,Vivian
中科院分区：
文献类型：
--
作者：
Robertson,GabriellaL;Romero-Morales,AlejandraI;Lippmann,EthanS;Gama,Vivian
发育生物学长期以来受益于经典模式生物的研究。这些模型系统提供了对发育一般原理的基本理解，以及对控制细胞命运规范和组织形态发生的独特方面的基因和信号通路的见解。由于人类大脑发育不能在体内进行研究，科学家们依靠这些模型系统来研究这个复杂器官发育的基本原理，因为许多这些基因和信号通路在人类发育中起着保守的作用。然而，最近的研究表明，神经发育中的物种特异性特征，如放射状外胶质细胞的转录组，表明使用人类衍生的模型仍然是必要的。在过去的十年中，人类干细胞衍生的脑类器官已经成为研究正常人脑发育和神经系统疾病的生物学相关模型系统。在这里，我们提供了这一新兴模型系统的历史视角，讨论了当前的系统和局限性，并提出可以利用这些三维大脑结构揭示细胞生物学的新机制。
Developmental biology has long benefited from studies of classic model organisms. These model systems have provided the fundamental understanding of general principles of development, as well as insight into genes and signaling pathways that control unique aspects of cell fate specification and tissue morphogenesis. Because human brain development cannot be studied in vivo, scientists have relied on these model systems to study basic principles underlying the development of this complex organ as many of these genes and signaling pathways play conserved roles in human development. However, recent studies have shown species-specific signatures in neurodevelopment such as the transcriptome of outer-radial glia, suggesting use of a human-derived model remains imperative. Over the past decade, human stem cell-derived brain organoids have emerged as a biologically relevant model system to study normal human brain development and neurological diseases. Here, we provide a historical perspective of this emerging model system, discuss current systems and limitations, and propose that new mechanistic insight into cell biology can be revealed using these three-dimensional brain structures.