Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates

Abstract

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.

Vertebrate Sensory Ganglia: Common and Divergent Features of the Transcriptional Programs Generating Their Functional Specialization

“…A model has been proposed in which multiple environmental cues act on developing axons of unspecified sensory neurons. Depending on the timing and trajectories of their projection patterns, these cues resolve the TF expression patterns of newborn somatosensory neurons from a coexpressed state to a subtype-restricted state, which allows their molecular, morphological and electrophysiological specialization (Faure et al, 2020;Sharma et al, 2020). How this switch occurs during cell fate decisions in neural crest remains unknown.…”

An Integrated View on Neuronal Subsets in the Peripheral Nervous System and Their Role in Immunoregulation

“…Because of a significant heterogeneity in the degree of myelination and conduction velocity in functionally similar classes, this classification insufficiently reflects function. To gain further insight into different populations and to functionally discern the neurons within DRGs, there are now many studies available, which have performed single-cell RNA-sequencing and associated gene expression with a function in mice, primates and humans (12,(62)(63)(64)(65)(66)(67)(68). The respective datasets can be accessed via online tools and screened for genes of interest (as outlined in Table 2).…”

NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation

“…To further support our model, we queried important markers of nociceptor development, recently determined in mice as well as transcription factors found enriched in hDRG (26,45).…”

“…Developmental gene expression signatures and their regulation are currently only available for iPSC-derived cortical neurons (23,24). Protein-coding genes and long non-coding RNAs (lncRNAs) have been in the focus of recent gene expression studies during cell differentiation (25,26). At the same time, a critical role for a class of transcriptional regulators called microRNAs as hub regulators of pluripotency, balancing of cell fate decisions, as well as guiding of cell-cycle progression and self-renewal properties of human embryonic stem cells is emerging (27)(28)(29)(30)(31)(32)(33)(34).…”