Department of Biology, College of Arts and Sciences, Charlottesville, VA, USA.
Neuroscience Graduate Program, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Nat Neurosci. 2022 Nov;25(11):1543-1558. doi: 10.1038/s41593-022-01181-8. Epub 2022 Oct 27.
Precisely controlled development of the somatosensory system is essential for detecting pain, itch, temperature, mechanical touch and body position. To investigate the protein-level changes that occur during somatosensory development, we performed single-cell mass cytometry on dorsal root ganglia from C57/BL6 mice of both sexes, with litter replicates collected daily from embryonic day 11.5 to postnatal day 4. Measuring nearly 3 million cells, we quantified 30 molecularly distinct somatosensory glial and 41 distinct neuronal states across all timepoints. Analysis of differentiation trajectories revealed rare cells that co-express two or more Trk receptors and over-express stem cell markers, suggesting that these neurotrophic factor receptors play a role in cell fate specification. Comparison to previous RNA-based studies identified substantial differences between many protein-mRNA pairs, demonstrating the importance of protein-level measurements to identify functional cell states. Overall, this study demonstrates that mass cytometry is a high-throughput, scalable platform to rapidly phenotype somatosensory tissues.
精确控制躯体感觉系统的发育对于检测疼痛、瘙痒、温度、机械触觉和身体姿势至关重要。为了研究躯体感觉发育过程中发生的蛋白质水平变化,我们对 C57/BL6 雌雄小鼠的背根神经节进行了单细胞质量细胞术分析,每天从胚胎第 11.5 天到出生后第 4 天收集窝内重复样本。我们测量了近 300 万个细胞,在所有时间点定量分析了 30 种分子上不同的躯体感觉神经胶质和 41 种不同的神经元状态。分化轨迹分析显示出少数同时表达两种或更多 Trk 受体并过度表达干细胞标志物的细胞,这表明这些神经营养因子受体在细胞命运特化中发挥作用。与之前基于 RNA 的研究相比,许多蛋白质-mRNA 对之间存在显著差异,这表明蛋白质水平测量对于鉴定功能细胞状态非常重要。总的来说,这项研究表明,质量细胞术是一种高通量、可扩展的平台,可以快速表型化躯体感觉组织。