Single-cell transcription mapping of neural subtype development in human spinal cord

The spinal cord possesses precise neural circuitry to transmit messages between the brain and body. Detailed transcriptomic profiling of the developing human spinal cord has not been reported. Here, we performed single cell RNA sequencing of developing human spinal cord cells and compared these data with similar mouse spinal cord RNA sequencing datasets. The differentiation tendency of proliferative neural progenitor cells changed from neuronal to glial cells at gestational week (GW) 8 and we identified a diverse set of excitatory, inhibitory and motor neuron cell types. Human ventral neuronal differentiation occurred earlier than GW7, while DI4/5 interneurons are born between GW7–11. We identified glial cell molecular diversity and revealed that ependymal cell specification occurs before birth. We also demonstrate differences between human and mouse spinal cord, including unique cell subtypes, gene expression, neurotransmitter receptors, and glial differentiation timing. Our results offer insight into human spinal cord development. Overall design: Here we performed both nucleus single-cell RNA sequencing and cellular single-cell RNA sequencing analyses of more than 880,000 cells isolated from the human spinal cord at gestation week 7 to 25.

脊髓具备精密的神经环路，可在大脑与机体之间传递神经信号。目前尚无针对发育中人脊髓的详细转录组分析（transcriptomic profiling）相关报道。本研究对发育中的人脊髓细胞进行了单细胞RNA测序（single cell RNA sequencing），并将所得数据与已发表的小鼠脊髓RNA测序数据集进行了比对分析。增殖性神经前体细胞的分化倾向在第8孕周（GW）时从神经元转向胶质细胞；本研究鉴定出了一系列多样化的兴奋性、抑制性及运动神经元细胞亚型。人腹侧神经元的分化早于第7孕周，而DI4/5中间神经元则诞生于第7至11孕周之间。本研究还揭示了胶质细胞的分子多样性，并证实室管膜细胞的特化发生于出生前。此外，本研究还发现了人与小鼠脊髓之间的多项差异，包括独特的细胞亚型、基因表达谱、神经递质受体特征及胶质细胞分化时序。本研究结果为人类脊髓发育研究提供了重要见解。实验设计概况：本研究对7至25孕周期间分离自人脊髓的超过88万个细胞，同时开展了单细胞细胞核RNA测序与单细胞完整细胞RNA测序分析。