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Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain [Macaque snRNA-seq]

ABSTRACT: Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain [Macaque snRNA-seq]

PROVIDER: PRJNA1067990 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27693285_1.fastq.gz	Fastqsanger.gz
	SRR27693285_2.fastq.gz	Fastqsanger.gz
	SRR27693286_1.fastq.gz	Fastqsanger.gz
	SRR27693286_2.fastq.gz	Fastqsanger.gz
	SRR27693287_1.fastq.gz	Fastqsanger.gz

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Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain [Macaque snRNA-seq]

Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.

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Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain [Mouse Xenium]

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snRNA-seq of macaque (Macaca mulatta) adult testis

Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 7,631 nuclei in macaque adult testis. This dataset includes two samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.

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Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain.

Project description:Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain.

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A human microphysiological model of afferent DRG nociceptor-spinal cord dorsal horn circuitry

Project description:We generated single cell RNA-seq data to measure the transctiptional profiles of cervicothoracic human pluripotent stem cell-derived dorsal horn spheroids cultured together with human DRG spheroids in an in-vitro model of the dorsal root ganglion-spinal horn dorsal horn pain circuit. hPSC derived dorsal horn interneurons were generated using our previously established protocol and aggregated into spheroids. These spheroids were cultured in a microphysiological device for 5 weeks together with human DRG spheroids created using hiPSC derived nociceptors purchased from Anatomic Inc. In toal we recovered the transcriptomes of 28,445 cells. Analysis verified the presence of the dI4/dI5 cells of the superficial dorsal horn which are implicated in the modeled pain circuit. These cells also expressed a high level of late-born neuronal markers NFIB and Neurod2.

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