Transcriptome profiles of distinct mechanoreceptive somatosensory neuron subtypes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE127161 | GEO | 2019/03/31
REPOSITORIES: GEO
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Project description:During development neurons achieve a high degree of specialization (Fishell and Heintz, 2013). Over time, while continuously recycling their components and despite transcriptional noise, their own respective properties remain intact. The transcription factors that play a large role in initially establishing neuronal identity can be required for maintaining it (Deneris and Hobert, 2014). Post-transcriptional regulation is also important to differentiation (Bian and Sun, 2011) but its role in maintaining cell identity is less established. To better understand how post-transcriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory class, whose properties are well established and display clear differences when compared to other neurons in the ganglion. By conditionally ablating Dicer in mice, using a parvalbumin (Pvalb) driven cre, we impaired post-transcriptional regulation in the proprioceptive sensory neuron population. KO animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is mirrored by a cell-death within the DRG. Before cell-loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of non-proprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Post-transcriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons.
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Project description:Cutaneous C-unmyelinated free nerve endings and hair follicles-innervating C-LTMRs convey two opposite aspects of touch sensation: a sensation of pain and a sensation of pleasant touch. The molecular mechanisms underlying these diametrically opposite functions are unknown. Here we used a mouse model that genetically marks C-LTMRs and the free nerve endings MRGPRD+ neurons in combination with fluorescent cell surface labeling, flow cytometry and RNA deep-sequencing technology. Cluster analysis of the RNA-Seq profiles of the purified neuronal subsets revealed 156 and 184 genes differentially expressed in MRGPRD-expressing neurons and C-LTMRs, respectively. 48 MRGPD- and 67 C-LTMRs-enriched genes were validated using a triple staining experiment approach and the Cav3.3 channel, found to be exclusively expressed in C-LTMRs, was validated using electrophysiology. Furthermore, our study greatly expands the molecular characterization of C-LTMRs and suggests that this particular population of neurons shares common transcriptional signatures with A and A low threshold mechanoreceptors.
2015-02-01 | GSE64091 | GEO
Project description:Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. RNA-seq of mRNA levels in 197 individual DRG neurons We performed RNA-seq on total 203 individual DRG neurons. Six of them were not qualified and thus, were excluded for further analysis. To evaluate the quality of RNA-seq, we randomly devided No.72 neurons into two parts and performed RNA-seq seperately. Thus, we had 204 individual samples from 203 individual DRG and 198 individual qualified samples from 197 individual DRG. To evaluate the homogeneity of RNA-seq data from different mice at the same age just as used, we performed RNA-seq on 5 single DRG from different mice. Here, these data from DRG were also considered as experimental control. The 'DRG_neurons_RNA_Seq.txt' contains processed data for 204 samples and 'DRG_RNA_Seq.txt' for 5 samples.
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