A harmonized atlas of mouse spinal cord cell types and their spatial organization

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Сен. 29, 2021

Abstract Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases mouse spinal cord have been published in recent years but not integrated together. Here, we generate an atlas types based on single-cell transcriptomic data, unifying available datasets into a common reference framework. We report hierarchical structure postnatal relationships, with location providing highest level organization, then neurotransmitter status, family, and finally, dozens refined populations. validate combinatorial marker code for each neuronal map their spatial distributions adult cord. also show complex lineage relationships among Additionally, develop open-source classifier, SeqSeek, to facilitate standardization identification. This work provides view types, gene expression signatures, organization.

Язык: Английский

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Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

Neuron, Год журнала: 2020, Номер 109(1), С. 73 - 90.e7

Опубликована: Ноя. 11, 2020

Язык: Английский

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Brain circuits for pain and its treatment

Science Translational Medicine, Год журнала: 2021, Номер 13(619)

Опубликована: Ноя. 10, 2021

Understanding the organization of brain’s pain circuits is critical for developing effective treatments patients suffering from chronic pain.

Язык: Английский

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A cellular taxonomy of the adult human spinal cord

Neuron, Год журнала: 2023, Номер 111(3), С. 328 - 344.e7

Опубликована: Фев. 1, 2023

The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding cellular diversity, characterizing human biology directly is important to uncover specialized features basic function pathology. Here, we present taxonomy the adult using single-nucleus RNA sequencing with spatial transcriptomics antibody validation. We identified 29 glial clusters 35 neuronal clusters, organized principally by anatomical location. To demonstrate relevance this resource disease, analyzed motoneurons, which degenerate in amyotrophic lateral sclerosis (ALS) other diseases. found that compared neurons, motoneurons are defined genes related size, cytoskeletal structure, ALS, suggesting molecular repertoire underlying their selective vulnerability. include web facilitate further investigations into biology.

Язык: Английский

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Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

Science Advances, Год журнала: 2024, Номер 10(25)

Опубликована: Июнь 21, 2024

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli central nervous system. Single-cell RNA sequencing has provided insights into diversity of sensory ganglia cell types rodents, nonhuman primates, humans, but it remains difficult compare across studies species. We thus constructed harmonized atlases DRG TG that describe facilitate comparison 18 neuronal 11 non-neuronal six species 31 datasets. then performed single-cell/nucleus from both human highly regenerative axolotl found atlas also improves type annotation, particularly sparse subtypes. observed transcriptomes neuron subtypes broadly similar vertebrates, expression functionally important neuropeptides channels can vary notably. The resources presented here guide future comparative transcriptomics, simplify cell-type nomenclature differences studies, help prioritize targets for analgesic development.

Язык: Английский

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A functional subdivision within the somatosensory system and its implications for pain research

Neuron, Год журнала: 2022, Номер 110(5), С. 749 - 769

Опубликована: Янв. 10, 2022

Язык: Английский

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Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

Journal of Neuroscience, Год журнала: 2021, Номер 41(5), С. 845 - 854

Опубликована: Янв. 20, 2021

Spinal interneurons are important facilitators and modulators of motor, sensory, autonomic functions in the intact CNS. This heterogeneous population neurons is now widely appreciated to be a key component plasticity recovery. review highlights our current understanding spinal interneuron heterogeneity, their contribution control modulation motor sensory functions, how this role might change after traumatic cord injury. We also offer perspective for treatments can optimize functional improvement.

Язык: Английский

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Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 5, 2023

Abstract Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli including touch, temperature, pain central nervous system. Recent advances single-cell RNA-sequencing (scRNA-seq) have provided new insights into diversity of ganglia cell types rodents, non-human primates, humans, but it remains difficult compare transcriptomically defined across studies species. Here, we built cross-species harmonized atlases DRG TG that describe 18 neuronal 11 non-neuronal 6 species 19 studies. We then demonstrate utility this reference atlas by using annotate newly profiled nuclei/cells from both human highly regenerative axolotl. observe transcriptomic profiles neuron subtypes broadly similar vertebrates, expression functionally important neuropeptides channels can vary notably. The resources data presented here guide future comparative transcriptomics, simplify type nomenclature differences studies, help prioritize targets for therapy development.

Язык: Английский

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Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn

eLife, Год журнала: 2023, Номер 12

Опубликована: Фев. 7, 2023

Spinally projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how mediate these opposing effects. Utilizing virus-based strategies Tph2-Cre transgenic mice, we identified two anatomically separated populations of hindbrain located the lateral paragigantocellularis (LPGi) medial hindbrain, which respectively innervate superficial deep spinal dorsal horn have contrasting effects sensory perception. Our tracing experiments revealed that LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than neurons. Taking advantage this difference, employed intersectional chemogenetic approaches demonstrate activation projections decreases thermal sensitivity, whereas increases mechanical von Frey stimulation. Together results suggest there are functionally distinct classes differ their anatomical location postsynaptic targets cord, impact nociceptive sensitivity. The give rise rather global bilateral throughout rostrocaudal extent cord appear be ideally poised contribute widespread systemic control.

Язык: Английский

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Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn

Neuron, Год журнала: 2024, Номер 112(8), С. 1302 - 1327.e13

Опубликована: Март 6, 2024

Язык: Английский

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