Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Abstract The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neu...

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Autores principales:	Alexander Chamessian, Michael Young, Yawar Qadri, Temugin Berta, Ru-Rong Ji, Thomas Van de Ven
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dcce6c06a46d4e4693ba993145a38ed0
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spelling	oai:doaj.org-article:dcce6c06a46d4e4693ba993145a38ed02021-12-02T15:09:04ZTranscriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn10.1038/s41598-018-25110-72045-2322https://doaj.org/article/dcce6c06a46d4e4693ba993145a38ed02018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25110-7https://doaj.org/toc/2045-2322Abstract The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice. Using RNA-sequencing (RNA-seq), we uncovered more than 13,000 genes. Differential gene expression analysis revealed more than 900 genes with at least 2-fold enrichment. In addition to many known dorsal horn genes, we identified and validated several novel transcripts from pharmacologically tractable functional classes: Carbonic Anhydrase 12 (Car12), Phosphodiesterase 11 A (Pde11a), and Protease-Activated Receptor 3 (F2rl2). In situ hybridization of these novel genes showed differential expression patterns in the SDH, demonstrating the presence of transcriptionally distinct subpopulations within the SST population. Overall, our findings provide new insights into the gene repertoire of SST dorsal horn neurons and reveal several novel targets for pharmacological modulation of this pain-mediating population and treatment of pathological pain.Alexander ChamessianMichael YoungYawar QadriTemugin BertaRu-Rong JiThomas Van de VenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexander Chamessian Michael Young Yawar Qadri Temugin Berta Ru-Rong Ji Thomas Van de Ven Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
description	Abstract The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice. Using RNA-sequencing (RNA-seq), we uncovered more than 13,000 genes. Differential gene expression analysis revealed more than 900 genes with at least 2-fold enrichment. In addition to many known dorsal horn genes, we identified and validated several novel transcripts from pharmacologically tractable functional classes: Carbonic Anhydrase 12 (Car12), Phosphodiesterase 11 A (Pde11a), and Protease-Activated Receptor 3 (F2rl2). In situ hybridization of these novel genes showed differential expression patterns in the SDH, demonstrating the presence of transcriptionally distinct subpopulations within the SST population. Overall, our findings provide new insights into the gene repertoire of SST dorsal horn neurons and reveal several novel targets for pharmacological modulation of this pain-mediating population and treatment of pathological pain.
format	article
author	Alexander Chamessian Michael Young Yawar Qadri Temugin Berta Ru-Rong Ji Thomas Van de Ven
author_facet	Alexander Chamessian Michael Young Yawar Qadri Temugin Berta Ru-Rong Ji Thomas Van de Ven
author_sort	Alexander Chamessian
title	Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
title_short	Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
title_full	Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
title_fullStr	Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
title_full_unstemmed	Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
title_sort	transcriptional profiling of somatostatin interneurons in the spinal dorsal horn
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/dcce6c06a46d4e4693ba993145a38ed0
work_keys_str_mv	AT alexanderchamessian transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn AT michaelyoung transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn AT yawarqadri transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn AT temuginberta transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn AT rurongji transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn AT thomasvandeven transcriptionalprofilingofsomatostatininterneuronsinthespinaldorsalhorn
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Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

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