Single cell RNA-seq of great ape cerebral organoids. Single cell RNA-seq of great ape cerebral organoids

The human brain has changed dramatically from other primate species, but the genetic and developmental mechanisms behind the differences remains unclear. Here we used single cell RNA sequencing based on 10X technology to explore temporal transcriptomic dynamics and cellular heterogeneity in cerebral organoids derived from human and non-human primates chimpanzee and rhesus macaque stem cells. Using cerebral organoids as a proxy of early brain development, we detect a delayed pace of human brain development relative to the other two primate species. Additional human-specific gene expression patterns resolved to different cell states through progenitors to neurons are also found. Our data provide a transcriptomic cell atlas of primate early brain development, and illustrate features that are unique to humans.

人类大脑与其他灵长类物种相比已发生显著演化差异，但其背后的遗传与发育机制仍未明确。本研究基于10X技术（10X technology）开展单细胞RNA测序（single cell RNA sequencing），对源自人类与非人类灵长类（黑猩猩（chimpanzee）、恒河猴（rhesus macaque））的干细胞所构建的大脑类器官（cerebral organoids）进行分析，以探究其时间维度的转录组动态变化与细胞异质性。以大脑类器官作为早期脑发育的替代模型，本研究发现相较于另外两种灵长类，人类大脑发育的节奏更为迟缓。研究还鉴定出一系列人类特有的基因表达模式，这些模式在从神经祖细胞到神经元的不同细胞状态中均有体现。本研究的数据构建了灵长类早期脑发育的转录组细胞图谱，并揭示了人类大脑所特有的发育特征。