Lu Tian, Wang Mengdi, Zhou Wei, Ni Qi, Yue Yuanlei, Wang Wei, Shi Yingchao, Liu Zeyuan, Li Changlin, Hong Bei, Zhou Xin, Zhong Suijuan, Wang Kaikai, Zeng Bo, Zhang Jun, Wang Wei, Zhang Xu, Wu Qian, Wang Xiaoqun
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Cognitive Neuroscience and Learning, New Cornerstone Science Laboratory, Beijing Normal University, Beijing 100875, China; IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Cell. 2024 Dec 26;187(26):7374-7393.e28. doi: 10.1016/j.cell.2024.10.023. Epub 2024 Nov 12.
Dorsal root ganglia (DRGs) play a crucial role in processing sensory information, making it essential to understand their development. Here, we construct a single-cell spatiotemporal transcriptomic atlas of human embryonic DRG. This atlas reveals the diversity of cell types and highlights the extrinsic signaling cascades and intrinsic regulatory hierarchies that guide cell fate decisions, including neuronal/glial lineage restriction, sensory neuron differentiation and specification, and the formation of neuron-satellite glial cell (SGC) units. Additionally, we identify a human-enriched NTRK3/DCC nociceptor subtype, which is involved in multimodal nociceptive processing. Mimicking the programmed activation of signaling pathways in vivo, we successfully establish functional human DRG organoids and underscore the critical roles of transcriptional regulators in the fate commitment of unspecialized sensory neurons (uSNs). Overall, our research elucidates the multilevel signaling pathways and transcription factor (TF) regulatory hierarchies that underpin the diversity of somatosensory neurons, emphasizing the phenotypic distinctions in human nociceptor subtypes.
背根神经节（DRG）在处理感觉信息中起关键作用，因此了解其发育至关重要。在此，我们构建了人类胚胎DRG的单细胞时空转录组图谱。该图谱揭示了细胞类型的多样性，并突出了指导细胞命运决定的外在信号级联和内在调控层次，包括神经元/胶质细胞谱系限制、感觉神经元分化和特化，以及神经元-卫星胶质细胞（SGC）单元的形成。此外，我们鉴定出一种人类富集的NTRK3/DCC伤害感受器亚型，其参与多模式伤害性处理。模仿体内信号通路的程序性激活，我们成功建立了功能性人类DRG类器官，并强调了转录调节因子在未特化感觉神经元（uSN）命运决定中的关键作用。总体而言，我们的研究阐明了支持躯体感觉神经元多样性的多层次信号通路和转录因子（TF）调控层次，强调了人类伤害感受器亚型的表型差异。
