Department of Neurology, University of California, San Francisco, CA 94143.
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 2021 Jun 29;118(26). doi: 10.1073/pnas.2019415118.
Studies of the spatiotemporal, transcriptomic, and morphological diversity of radial glia (RG) have spurred our current models of human corticogenesis. In the developing cortex, neural intermediate progenitor cells (nIPCs) are a neuron-producing transit-amplifying cell type born in the germinal zones of the cortex from RG. The potential diversity of the nIPC population, that produces a significant portion of excitatory cortical neurons, is understudied, particularly in the developing human brain. Here we explore the spatiotemporal, transcriptomic, and morphological variation that exists within the human nIPC population and provide a resource for future studies. We observe that the spatial distribution of nIPCs in the cortex changes abruptly around gestational week (GW) 19/20, marking a distinct shift in cellular distribution and organization during late neurogenesis. We also identify five transcriptomic subtypes, one of which appears at this spatiotemporal transition. Finally, we observe a diversity of nIPC morphologies that do not correlate with specific transcriptomic subtypes. These results provide an analysis of the spatiotemporal, transcriptional, and morphological diversity of nIPCs in developing brain tissue and provide an atlas of nIPC subtypes in the developing human cortex that can benchmark in vitro models of human development such as cerebral organoids and help inform future studies of how nIPCs contribute to cortical neurogenesis.
对放射状胶质细胞 (RG) 的时空、转录组和形态多样性的研究推动了我们目前对人类皮质发生的模型。在发育中的皮质中,神经中间前体细胞 (nIPC) 是一种产生神经元的过渡扩增细胞类型,从皮质的生发区由 RG 产生。nIPC 群体产生的潜在多样性,产生了相当一部分兴奋性皮质神经元,目前研究不足,特别是在发育中的人类大脑中。在这里,我们探索了人类 nIPC 群体中存在的时空转录组和形态变化,并为未来的研究提供了资源。我们观察到,nIPC 在皮质中的空间分布在孕龄 19/20 周左右突然发生变化,标志着神经发生后期细胞分布和组织的明显转变。我们还鉴定出五个转录组亚型,其中一个出现在这个时空转换中。最后,我们观察到 nIPC 形态的多样性与特定的转录组亚型不相关。这些结果提供了对发育中脑组织中 nIPC 的时空、转录和形态多样性的分析,并提供了发育中人类皮质中 nIPC 亚型的图谱,可作为脑类器官等体外人类发育模型的基准,并有助于了解 nIPC 如何促进皮质神经发生。