Disentangling neural cell diversity using single-cell transcriptomics

Nature Neuroscience, Journal Year: 2016, Volume and Issue: 19(9), P. 1131 - 1141

Published: Aug. 26, 2016

Language: Английский

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Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq–based resource for pain and sensory neuroscience research

Pain, Journal Year: 2018, Volume and Issue: 159(7), P. 1325 - 1345

Published: March 20, 2018

Abstract Molecular neurobiological insight into human nervous tissues is needed to generate next-generation therapeutics for neurological disorders such as chronic pain. We obtained dorsal root ganglia (hDRG) samples from organ donors and performed RNA-sequencing (RNA-seq) study the hDRG transcriptional landscape, systematically comparing it with publicly available data a variety of orthologous mouse tissues, including DRG (mDRG). characterized profile in terms tissue-restricted gene coexpression patterns putative regulators, formulated an information-theoretic framework quantify enrichment. Relevant families pathways were also analyzed, transcription factors, G-protein-coupled receptors, ion channels. Our analyses reveal hDRG-enriched protein-coding set (∼140), some which have not been described context or pain signaling. Most these show conserved enrichment mDRG mined known drug–gene product interactions. Conserved vast majority factors suggests that faithful model system studying hDRG, because evolutionarily regulatory programs. Comparison tibial nerve transcriptomes trafficking neuronal mRNA axons adult are consistent studies axonal transport rodent sensory neurons. present our work online, searchable repository (https://www.utdallas.edu/bbs/painneurosciencelab/sensoryomics/drgtxome), creating valuable resource community. provide biology guiding development novel blueprint cross-species transcriptomic analyses.

Language: Английский

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Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Feb. 22, 2018

Single-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases analytic variability inherent current pipelines may undermine its replicability. Meta-analysis is further hampered by use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that quantifies degree which types replicate across datasets, enables rapid identification clusters with high similarity. We first measure replicability neuronal identity, comparing results eight technically biologically diverse datasets define best practices for more complex assessments. then apply this novel interneuron subtypes, finding 24/45 subtypes have evidence replication, robust candidate marker genes. Across tasks find large sets variably expressed genes can identify replicable accuracy, suggesting general route forward large-scale evaluation scRNA-seq data.

Language: Английский

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Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties

Neuron, Journal Year: 2019, Volume and Issue: 103(4), P. 598 - 616.e7

Published: June 24, 2019

Language: Английский

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Specialized cutaneous Schwann cells initiate pain sensation

Science, Journal Year: 2019, Volume and Issue: 365(6454), P. 695 - 699

Published: Aug. 15, 2019

An essential prerequisite for the survival of an organism is ability to detect and respond aversive stimuli. Current belief that noxious stimuli directly activate nociceptive sensory nerve endings in skin. We discovered a specialized cutaneous glial cell type with extensive processes forming mesh-like network subepidermal border skin conveys thermal mechanical sensitivity. demonstrate direct excitatory functional connection neurons provide evidence previously unknown organ has physiological role sensing Thus, these cells, which are intimately associated unmyelinated nerves, inherently mechanosensitive transmit information nerve.

Language: Английский

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The mechanosensory neurons of touch and their mechanisms of activation

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(9), P. 521 - 537

Published: July 26, 2021

Language: Английский

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In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(3), P. 440 - 446

Published: Jan. 12, 2018

Language: Английский

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Advances in understanding nociception and neuropathic pain

Journal of Neurology, Journal Year: 2017, Volume and Issue: 265(2), P. 231 - 238

Published: Oct. 14, 2017

Pain results from the activation of a subset sensory neurones termed nociceptors and has evolved as "detect protect" mechanism. However, lesion or disease in system can result neuropathic pain, which serves no protective function. Understanding how nervous works what changes occur pain are vital identifying new therapeutic targets developing novel analgesics. In recent years, technologies such optogenetics RNA-sequencing have been developed, alongside more traditional use animal models insights genetic variations humans enabled significant advances to be made mechanistic understanding pain.

Language: Английский

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Single-cell RNAseq reveals seven classes of colonic sensory neuron

Gut, Journal Year: 2018, Volume and Issue: 68(4), P. 633 - 644

Published: Feb. 26, 2018

Objective Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology organism behaviour. Colonic sensory neurons activate reflex pathways give rise to conscious sensation, but diversity division function within these is poorly understood. The identification signalling contributing visceral sensation constrained by a paucity molecular markers. Here we address this comprehensive transcriptomic profiling unsupervised clustering individual mouse colonic neurons. Design Unbiased single-cell RNA-sequencing was performed on retrogradely traced isolated from both thoracolumbar (TL) lumbosacral (LS) dorsal root ganglia associated with lumbar splanchnic pelvic spinal pathways, respectively. Identified neuronal subtypes were validated qRT-PCR, immunohistochemistry (IHC) Ca 2+ -imaging. Results Transcriptomic 314 revealed seven subtypes. Of these, five accounted for 99% TL neurons, LS almost exclusively populating remaining two We identify classify based novel subtype-specific marker genes using qRT-PCR IHC validate derived RNA-sequencing. Lastly, functional -imaging conducted demonstrate subtype-selective differential agonist activation. Conclusions unbiased confirm translation patterning protein expression, describing encompassing all modalities sensitivity. These results provide pathway interrogation innervation in health disease, together identifying targets drug development.

Language: Английский

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Circuit dissection of the role of somatostatin in itch and pain

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(5), P. 707 - 716

Published: March 19, 2018

Language: Английский

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