The research team of Wang Xiaoqun, a researcher from the Institute of Biophysics, Chinese Academy of Sciences, the research team of Zhang Xu, an academician of the Guangdong Institute of Intelligent Science and Technology, and the research team of Wu Qian, a professor of Beijing Normal University, deeply analyzed the multi-level signal pathways regulating the differentiation of multiple sensory neurons during the development of the human dorsal root ganglion (DRG), and successfully constructed the model of human DRG like organs (hDRGOs). The relevant paper was recently published in Cell. DRG is a gathering place for sensory neurons, responsible for transmitting sensory signals. Neural crest cells (NCC) can differentiate into various sensory neurons and glial cells in DRG, which requires precise regulation of specific signaling molecules and transcription factors. Previous studies have mostly been based on mouse models, but there are differences in subtypes and functional gene expression between human sensory neurons and mice. To construct the hDRGOs model, the research team used TF seq FISH technology to analyze human embryonic DRG development. They found that NCC produces two types of undifferentiated sensory neurons - uSN1 and uSN2- at critical time points, which are regulated by transcription factors and differentiate into large-diameter and small-diameter sensory cells, forming a diversity of sensory neurons. Based on these findings, researchers successfully constructed hDRGOs by incorporating signal factors in a temporal manner. These organoids replicate the differentiation process from pluripotent stem cells to sensory neurons, including the three main types of sensory neurons in DRG. These neurons are similar to human DRG in terms of developmental trajectory, gene expression, and physiological response. By comparing the development of sensory neurons in humans and mice, researchers found differences in their developmental processes, gene expression profiles, and cell subtypes. They also discovered subtypes of nociceptors specifically enriched in human DRGs, which are present in both developmental and adult DRGs and have been replicated in hDRGOs. Further experiments have confirmed that these sensory neurons can be specifically activated by capsaicin. This study not only provides important spatiotemporal transcriptome data for human embryonic DRG research, but also successfully establishes the hDRGOs model. This model is of great significance for studying the development of sensory neurons and related diseases, providing new tools and perspectives for future research. (New Society)
Edit：Yao jue Responsible editor：Xie Tunan
Source：China Science Daily
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