Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia.
Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia.
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DOI：
10.1038/s41593-020-00794-1
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发表时间：
2021-04
影响因子：
25
通讯作者：
Kriegstein AR
中科院分区：
文献类型：
--
作者：
Eze UC;Bhaduri A;Haeussler M;Nowakowski TJ;Kriegstein AR
人类大脑皮层由不同类型的细胞组成，这些细胞来自最初统一的神经上皮，形成放射状胶质细胞，即大脑皮层的神经干细胞。为了描述人类大脑发育的早期阶段，我们对人类大脑发育的各个区域进行了单细胞RNA测序，包括端脑、间脑、中脑、后脑和小脑。我们确定了9个在端脑附近的祖细胞群体，这表明比之前描述的更具异质性，包括一个非常普遍的间充质样群体，一旦神经发生开始就消失了。对相应阶段的人类和小鼠的祖细胞种群进行比较，确定了在人类皮质发育的早期阶段丰富的两个祖细胞簇。我们还发现，器官系统对神经上皮细胞和早期放射状胶质细胞类型的保真度较低，但随着神经发生的进展而改善。总体而言，我们提供了人类大脑和皮质发育早期的全面分子和空间图谱。Eze等人。使用单细胞测序和免疫组织化学验证来创建人类早期大脑发育的图谱。在端脑中，他们发现了多种祖细胞亚型，其中包括两种在人类中丰富的亚型。
The human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development. Eze et al. use single-cell sequencing and immunohistochemical validation to create an atlas of early human brain development. In the telencephalon, they discover a diversity of progenitor subtypes, including two that are enriched in humans.
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