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Derivation and analysis of human somatic sensory neuron subtypes facilitated through fluorescent hPSC reporters

ABSTRACT: Peripheral sensory neuropathy (PSN) is associated with several devastating neurological conditions, yet effective strategies to prevent or alleviate the consequences of PSN are nearly non-existent. A major challenge in the development of better therapeutic interventions is the lack of appropriate human model systems. Human induced pluripotent stem cell (hiPSC)-derived somatosensory neurons present a promising strategy to overcome this issue but remain of limited translational utility, in part due to the low efficiency and lack of sensory subtype selectivity of the existing sensory neuron derivation protocols. To improve upon iPSC-based somatosensory disease models, we here describe the generation and validation of a genetic toolset to fluorescently label all or distinct (nociceptor, low threshold mechanoreceptor, and proprioceptor) somatosensory subtypes. These new resources will be transformative for hPSC-based approaches in PSN disease modeling - a critical step towards translating new findings into clinically relevant therapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE310583 | GEO | 2026/03/04

REPOSITORIES: GEO

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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 Â± 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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Derivation and analysis of human somatic sensory neuron subtypes facilitated through fluorescent hPSC reporters

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