A developmental atlas of somatosensory diversification and maturation in the dorsal root ganglia by single-cell mass cytometry

Abstract

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, with litter replicates collected daily from E11.5 to P4. Measuring nearly 3 million cells, we quantified 30 molecularly distinct somatosensory glial and 41 distinct neuronal states across all time points. Analysis of differentiation trajectories revealed rare cells that coexpress two or more Trk receptors and overexpress 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.

A developmental atlas of the mouse brain by single-cell mass cytometry

“…7b). This observation is similar to that of presumptive cargos in immature satellite glial cells by mass cytometry 46 , and identification of mRNAs for MBP and GFAP in P7 microglia by scRNAseq 130 .…”

“…the dorsal root ganglia 46 , a fortuitous result of this study was the observation of putative phagocytic cargoes in microglia. Phagocytosis by microglia plays an important role in brain development 147,148,134 , homeostasis 130 , injury 149 , and disease 150 .…”

“…The antibody-based measurements from mass cytometry can directly read out functional biomolecules, unlike mRNA transcripts that do not necessarily correlate with protein abundancea disconnect most pronounced during dynamic cell transitions 28,29 like those occurring in early brain development. Mass cytometry was previously employed to investigate glioma [30][31][32][33][34][35][36][37] , microglia [38][39][40][41][42][43][44][45] , and dorsal root ganglia 46 , but this approach has not yet been applied to study neural cell types in the brain, except for one limited analysis with seven neural-specific markers in a study of obesity-inhibited adult neurogenesis 47 .…”