中国科学院生物物理研究所王晓群等研究人员，合作解码发育中人类感觉神经元的转录身份及类器官建模。这一研究成果于2024年11月12日在线发表在国际学术期刊《细胞》上。
研究人员构建了一个人类胚胎背根神经节（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，并突出了引导细胞命运决策的外部信号级联反应和内部调控层次，包括神经元/胶质系谱限制、感觉神经元分化与特化，以及神经元-卫星胶质细胞（SGC）单元的形成。
此外，研究人员还识别出一种在人类中富集的NTRK3+/DCC+疼痛感受器亚型，参与多模态的痛觉处理。通过模拟体内信号通路的程序化激活，研究人员成功建立了具有功能的DRG类器官，并强调了转录调控因子在未特化感觉神经元（uSN）命运承诺中的关键作用。
总体而言，该研究阐明了支撑躯体感觉神经元多样性的多层级信号通路和转录因子（TF）调控层次，并强调了人类疼痛感受器亚型的表型差异。
据悉，DRG在处理感觉信息中发挥着至关重要的作用，因此了解其发育过程至关重要。
附：英文原文
Title: Decoding transcriptional identity in developing human sensory neurons and organoid modeling
Author: Tian Lu, Mengdi Wang, Wei Zhou, Qi Ni, Yuanlei Yue, Wei Wang, Yingchao Shi, Zeyuan Liu, Changlin Li, Bei Hong, Xin Zhou, Suijuan Zhong, Kaikai Wang, Bo Zeng, Jun Zhang, Wei Wang, Xu Zhang, Qian Wu, Xiaoqun Wang
Issue&Volume: 2024-11-12
Abstract: 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.
DOI: 10.1016/j.cell.2024.10.023
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01205-4