The dorsal root ganglion (DRG) is a cluster of cell bodies located in the dorsal root of the spinal cord, housing sensory neurons, plays critical roles in detecting external stimuli such as mechanical forces, temperature, itch, and noxious signals like pain. As being a potential therapeutic target for treating chronic pain, particularly neuropathic pain, understanding the development of human DRG and the mechanisms regulating sensory neuron differentiation is therefore crucial.

A collaborative research team led by Professor WANG Xiaoqun from the Institute of Biophysics at the Chinese Academy of Sciences and Beijing Normal University, Professor WU Qian from Beijing Normal University, and Professor ZHANG Xu from the Guangdong Academy of Intelligent Science and Technology, recently published an article in Cell on November 12, 2024, titled "Decoding transcriptional identity in developing human sensory neurons and organoid modeling", presenting groundbreaking insights into human DRG development.

Utilizing multiomics sequencing technologies, particularly TF-seqFISH, a single-cell spatial transcriptomics technology approach developed by WANG Xiaoqun's team, the researchers constructed the spatiotemporal transcriptomics atlas of human embryonic DRG development during early to mid-pregnancy. For the first time, they revealed the dynamic changes in cellular diversification and spatial organization within human DRG during critical developmental stages.

By tracing the differentiation trajectories of early NCC lineages, the researchers elucidated the external signaling pathways and internal transcription factors that regulate the cell type differentiation and specification.

Mimicking the programmed activation of signaling in vivo, they successfully establish functional human DRG organoids, which recapitulate differentiation progression from pluripotent stem cells to NCCs, sensory neuron progenitors, and mature sensory neurons, including the human enriched NTRK1+/NTRK3+/DCC+ nociceptor subtype in vivo.

Additionally, incorporating the DRG organoid model, the researchers validated the critical roles of various transcription factors in regulating sensory neuron specification, highlighting the value of organoids in studying human sensory system development and function.

Overall, this research provides valuable resource on studying human embryonic DRG development and has established a robust culture system for generating human DRG organoids. These progresses offer critical foundations for further investigations on exploring sensory system development and screening drug targets to treat sensory nervous system disorders, such as chronic pain and itch.

Figure. Spatiotemporal Development Mechanisms of Human Dorsal Root Ganglia and Organoid Modeling

（Image by WANG Xiaoqun's group）

Article link: https://doi.org/10.1016/j.cell.2024.10.023

Contact: WANG Xiaoqun

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

Email: xiaoqunwang@ibp.ac.cn

（Reported by Prof. WANG Xiaoqun's group）