What is a cell type and how to define it?

Cell, Год журнала: 2022, Номер 185(15), С. 2739 - 2755

Опубликована: Июль 1, 2022

Язык: Английский

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The mechanosensory neurons of touch and their mechanisms of activation

Nature reviews. Neuroscience, Год журнала: 2021, Номер 22(9), С. 521 - 537

Опубликована: Июль 26, 2021

Язык: Английский

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Single-nucleus transcriptomic analysis of human dorsal root ganglion neurons

eLife, Год журнала: 2021, Номер 10

Опубликована: Ноя. 26, 2021

Somatosensory neurons with cell bodies in the dorsal root ganglia (DRG) project to skin, muscles, bones, and viscera detect touch temperature as well mediate proprioception many types of interoception. In addition, somatosensory system conveys clinically relevant noxious sensations pain itch. Here, we used single nuclear transcriptomics characterize transcriptomic classes human DRG that these diverse stimuli. Notably, multiple have features resemble their mouse counterparts although expression genes considered important for sensory function often differed between species. More unexpectedly, identified several no clear equivalent other This dataset should serve a valuable resource community, example means focusing translational efforts on molecules conserved across

Язык: Английский

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The emergence and influence of internal states

Neuron, Год журнала: 2022, Номер 110(16), С. 2545 - 2570

Опубликована: Май 27, 2022

Язык: Английский

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A multidimensional coding architecture of the vagal interoceptive system

Nature, Год журнала: 2022, Номер 603(7903), С. 878 - 884

Опубликована: Март 16, 2022

Abstract Interoception, the ability to timely and precisely sense changes inside body, is critical for survival 1–4 . Vagal sensory neurons (VSNs) form an important body-to-brain connection, navigating visceral organs along rostral–caudal axis of body crossing surface–lumen into appropriate tissue layers 5,6 The brain can discriminate numerous signals through VSNs, but underlying coding strategy remains poorly understood. Here we show that VSNs code organ, layer stimulus modality—three key features interoceptive signal—in different dimensions. Large-scale single-cell profiling from seven major in mice using multiplexed projection barcodes reveals a ‘visceral organ’ dimension composed differentially expressed gene modules body’s axis. We discover another ‘tissue layer’ with locations VSN endings organs. Using calcium-imaging-guided spatial transcriptomics, are organized functional units similar stimuli across layers; this constitutes third ‘stimulus modality’ dimension. three independent feature-coding dimensions together specify many parallel pathways combinatorial manner facilitate complex brainstem. Our study highlights multidimensional architecture mammalian vagal system effective signal communication.

Язык: Английский

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A transcriptomic axis predicts state modulation of cortical interneurons

Nature, Год журнала: 2022, Номер 607(7918), С. 330 - 338

Опубликована: Июль 6, 2022

Abstract Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes 1–6 , but it is not known whether these have correspondingly diverse patterns activity in the living brain. Here we show primary visual cortex (V1) correlates with brain state, which are organized by single factor: position along main axis transcriptomic variation. We combined vivo two-photon calcium imaging mouse V1 method to identify mRNA for 72 selected genes ex slices. classified imaged layers 1–3 into three-level hierarchy 5 subclasses, 11 types and 35 using previously defined clusters 3 . Responses stimuli differed significantly only between cells Sncg subclass uniformly suppressed, other subclasses predominantly excited. Modulation state at all hierarchical levels could be largely predicted from first principal component, also correlations simultaneously recorded cells. Inhibitory fired more resting, oscillatory states had smaller fraction their axonal projections layer 1, narrower spikes, lower input resistance weaker adaptation as determined vitro 7 expressed cholinergic receptors. Subtypes during arousal opposite properties. Thus, simple principle may explain how shape state-dependent processing.

Язык: Английский

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Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine

Neuron, Год журнала: 2022, Номер 110(11), С. 1806 - 1821.e8

Опубликована: Март 28, 2022

Язык: Английский

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The Form and Function of PIEZO2

Annual Review of Biochemistry, Год журнала: 2021, Номер 90(1), С. 507 - 534

Опубликована: Июнь 20, 2021

Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) essential for a wide variety of processes, including our sense touch on skin. How detected transduced at molecular level has proved be one great mysteries sensory biology. A major breakthrough occurred in 2010 with discovery family mechanically gated ion channels that were coined PIEZOs. The last 10 years investigation have provided wealth information about functional roles mechanisms these molecules. Here we focus PIEZO2, two PIEZO proteins found humans other mammals. We review how work molecular, cellular, systems levels over past decade transformed understanding led unexpected insights into types mechanosensation beyond

Язык: Английский

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PIEZO2 in somatosensory neurons controls gastrointestinal transit

Cell, Год журнала: 2023, Номер 186(16), С. 3386 - 3399.e15

Опубликована: Авг. 1, 2023

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence food and help digestion mechanically breaking down propelling gut content. Mechanical sensing thought to be essential for regulating motility; however, identity neuronal populations, molecules involved, functional consequences this sensation unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel motility. Piezo2 mouse dorsal root, but not nodose ganglia required sense content, activity slows transit rates stomach, small intestine, colon. Indeed, directly detect colon distension vivo. Our study unveils mechanosensory mechanisms regulate luminal contents throughout gut, which critical process ensure proper digestion, nutrient absorption, waste removal.

Язык: Английский

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A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes

Cell, Год журнала: 2024, Номер 187(6), С. 1508 - 1526.e16

Опубликована: Март 1, 2024

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from periphery to CNS has been challenging with existing tools. Here, we develop curate mouse genetic toolkit that allows for interrogating properties functions distinct cutaneous targeting subtypes. These tools have enabled broad morphological analysis, which revealed axon arborization areas branching patterns transcriptionally Moreover, in vivo physiological analysis each subtype threshold range responses mechanical and/or thermal stimuli. findings support model morphologically physiologically sensory tile stimulus space collectively encode wide natural

Язык: Английский

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