Perspectives on single-nucleus RNA sequencing in different cell types and tissues

Journal of Pathology and Translational Medicine, Journal Year: 2023, Volume and Issue: 57(1), P. 52 - 59

Published: Jan. 10, 2023

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues alterations disease states. For certain cell types conditions, there are difficulties isolating intact cells transcriptome profiling due to their fragility, large size, tight interconnections, other factors. Single-nucleus (snRNA-seq) is an alternative or complementary approach that difficult isolate. In this review, we will provide overview of the experimental analysis steps snRNA-seq understand methods characteristics general tissue-specific data. Knowing advantages limitations increase its use improve biological interpretation data generated using technique.

Language: Английский

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The evolution of Big Data in neuroscience and neurology

Journal Of Big Data, Journal Year: 2023, Volume and Issue: 10(1)

Published: July 10, 2023

Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started transform fields Neuroscience Neurology. Scientists clinicians collaborating global alliances, combining diverse datasets a massive scale, solving complex computational problems that demand utilization increasingly powerful resources. This revolution is opening new avenues for developing innovative treatments neurological diseases. Our paper surveys Data's impact patient care, as exemplified through work done comprehensive selection areas, including Connectomics, Alzheimer's Disease, Stroke, Depression, Parkinson's Pain, Addiction (e.g., Opioid Use Disorder). We present an overview research methodologies utilizing each area, well their current limitations technical challenges. Despite potential benefits, full these currently remains unrealized. close with recommendations future aimed at optimizing use Neurology improved outcomes.The online version contains supplementary material available 10.1186/s40537-023-00751-2.

Language: Английский

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Large-scale neurophysiology and single-cell profiling in human neuroscience

Nature, Journal Year: 2024, Volume and Issue: 630(8017), P. 587 - 595

Published: June 19, 2024

Language: Английский

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Single-cell transcriptome profiles of Drosophila fruitless-expressing neurons from both sexes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 1, 2023

Drosophila melanogaster reproductive behaviors are orchestrated by fruitless neurons. We performed single-cell RNA-sequencing on pupal neurons that produce sex-specifically spliced fru transcripts, the P1-expressing Uniform Manifold Approximation and Projection (UMAP) with clustering generates an atlas containing 113 clusters. While male female overlap in UMAP space, more than half clusters have sex differences neuron number, nearly all display sex-differential expression. Based examination of enriched marker genes, we annotate as circadian clock neurons, mushroom body Kenyon cell neurotransmitter- and/or neuropeptide-producing, those express doublesex . Marker gene analyses also show genes encode members immunoglobulin superfamily adhesion molecules, transcription factors, neuropeptides, neuropeptide receptors, Wnts unique patterns expression across In vivo spatial links to examined. A functional analysis P1 shows they dimorphic roles activity period length. Given most comprised indicates sexes common programs. Sex-specific is overlaid this program, build potential for vastly different sex-specific behaviors.

Language: Английский

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Probing neural circuit mechanisms in Alzheimer’s disease using novel technologies

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4407 - 4420

Published: March 23, 2023

The study of Alzheimer's Disease (AD) has traditionally focused on neuropathological mechanisms that guided therapies attenuate features. A new direction is emerging in AD research focuses the progressive loss cognitive function due to disrupted neural circuit mechanisms. Evidence from humans and animal models show dysregulated circuits initiate a cascade pathological events culminate functional learning, memory, other aspects cognition. Recent progress single-cell, spatial, omics informs this circuit-focused approach by determining identities, locations, circuitry specific cells affected AD. Recently developed neuroscience tools allow for precise access cell type-specific so their roles AD-related deficits disease progression can be tested. An integrated systems-level understanding AD-associated requires multimodal multi-scale interrogations longitudinally measure and/or manipulate ensemble properties molecularly-defined neuron populations first susceptible These newly technological conceptual advances present opportunities studying treating vulnerable represent beginning era circuit-based research.

Language: Английский

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Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice

CNS Spectrums, Journal Year: 2023, Volume and Issue: 29(1), P. 26 - 39

Published: Sept. 7, 2023

Abstract Psychiatric disorders are associated with significant social and economic burdens, many of which related to issues current diagnosis treatments. The coronavirus (COVID-19) pandemic is estimated have increased the prevalence burden major depressive anxiety disorders, indicating an urgent need strengthen mental health systems globally. To date, approaches adopted in drug discovery development for psychiatric been relatively unsuccessful. Precision psychiatry aims tailor healthcare more closely needs individual patients and, when informed by neuroscience, can offer opportunity improve accuracy disease classification, treatment decisions, prevention efforts. In this review, we highlight growing global interest precision potential National Institute Health-devised Research Domain Criteria (RDoC) facilitate implementation transdiagnostic improved approaches. nosology evolve recent scientific advancements increase awareness emerging investigators/clinicians value approach essential. Finally, examine challenges future opportunities adopting RDoC-associated translational clinical studies, acknowledging that strength RDoC they form a dynamic framework guiding principles intended continuously developments into future. A collaborative recruits expertise from multiple disciplines, while also considering patient perspective, needed pave way prognosis quality life patients.

Language: Английский

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BRAIN @ 10: A decade of innovation

Neuron, Journal Year: 2024, Volume and Issue: 112(18), P. 3003 - 3006

Published: Sept. 1, 2024

Language: Английский

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The BRAIN initiative: a pioneering program on the precipice

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Language: Английский

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A full-body transcription factor expression atlas with completely resolved cell identities in C. elegans

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 9, 2024

Abstract Invariant cell lineage in C. elegans enables spatiotemporal resolution of transcriptional regulatory mechanisms controlling the fate each cell. Here, we develop RAPCAT (Robust-point-matching- And Piecewise-affine-based Cell Annotation Tool) to automate identity assignment three-dimensional image stacks L1 larvae and profile reporter expression 620 transcription factors every Transcription factor profile-based clustering analysis defines 80 types distinct from conventional phenotypic identifies three general modalities related these classifications. First, are broadly downregulated quiescent stage Hermaphrodite Specific Neurons, suggesting stage- type-specific variation transcriptome size. Second, is more closely associated with morphology than other different pre- post-differentiation developmental stages. Finally, embryonic lineages can be specific patterns functions that persist throughout postembryonic life. This study presents a comprehensive atlas for investigation intra-cell type heterogeneity.

Language: Английский

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Intravenous gene transfer throughout the brain of infant Old World primates using AAV

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 9, 2022

Abstract Adeno-associated viruses (AAVs) can enable robust and safe gene delivery to the mammalian central nervous system (CNS). While scientific community has developed numerous neurotropic AAV variants for systemic gene-transfer rodent brain, there are few AAVs that efficiently access CNS of higher order primates. We describe here AAV.CAP-Mac, an engineered variant enables systemic, brain-wide in infants two Old World primate species—the rhesus macaque ( Macaca mulatta ) green monkey Chlorocebus sabaeus ). identified CAP-Mac using a multi-species selection strategy, initially screening our library adult common marmoset Callithrix jacchus narrowing pool test-variants another round infant macaques. In individual characterization, robustly transduces human neurons vitro vivo , where it targets all lobes cortex, cerebellum, multiple subcortical regions disease relevance. use Brainbow-like multicolor labeling throughout enabling morphological reconstruction both medium spiny cortical pyramidal cells. Because its broad distribution brain high neuronal efficiency primates compared AAV9, shows promise researchers clinicians alike unlock novel, noninvasive efficient transfer.

Language: Английский

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