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    • Decoding Transcriptional Identity in Developing Human Sensory Neurons and Organoid Modeling

    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,Xu Zhang,Qian Wu,Xiaoqun Wang

    Cell（2024）

    Cited 0|Views7
    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.
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    Key words
    human dorsal root ganglia,sensory neuron,neurogenesis wave,transcription factors,signaling pathway,cross-species comparison,single-cell spatial transcriptome,nociceptor,TF-seqFISH,DRG organoid
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