Advancements in Single-Cell RNA Sequencing and Spatial Transcriptomics for Central Nervous System Disease DOI Creative Commons
Yuan Zhang, Teng Li, Guangtian Wang

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Oct. 10, 2024

The incidence of central nervous system (CNS) disease has persistently increased over the last several years. There is an urgent need for effective methods to improve cure rates CNS disease. However, precise molecular basis underlying development and progression major diseases remains elusive. A complete map will contribute research on treatment strategies. Emerging technologies such as single-cell RNA sequencing (scRNA-seq) Spatial Transcriptomics (ST) are potent tools exploring complexity, cell heterogeneity, functional specificity scRNA-seq ST can provide insights into at cellular spatial transcription levels. This review presents a survey studies diseases, chronic neurodegenerative acute injuries, others. These offer novel perspectives in treating diagnosing by discovering new types or subtypes associated with disease, proposing pathophysiological mechanisms, uncovering therapeutic targets, identifying putative biomarkers. Implications diseases. comprehensive understanding information context using ST, helping elucidate biological functions, intricate connection between crucial regulatory pathways, communication after

Language: Английский

Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping DOI Creative Commons
Di Zhang, Leslie A. Kirby, Yingxin Lin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 28, 2024

Abstract The ability to spatially map multiple layers of the omics information over different time points allows for exploring mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC–RNA–Protein-seq) CTRP-seq CUT&Tag– RNA–Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) dynamic remodeling development neuroinflammation. A spatiotemporal atlas mouse was obtained at stages from postnatal day P0 P21, compared regions interest human developing brains. Specifically, cortical area, discovered temporal persistence spreading chromatin accessibility layer-defining transcription factors. In corpus callosum, observed priming myelin genes across subregions. Together, it suggests a role layer specific projection neurons coordinate axonogenesis myelination. We further mapped lysolecithin (LPC) neuroinflammation model common molecular programs Microglia, exhibiting both conserved distinct inflammation resolution, are transiently activated not only core LPC lesion, but also distal locations presumably through neuronal circuitry. Thus, this work unveiled differential neuroinflammation, resulting valuable data resource investigate function

Language: Английский

Citations

16
4D marmoset brain map reveals MRI and molecular signatures for onset of multiple sclerosis–like lesions DOI
Jing‐Ping Lin, Alexis Brake, Maxime Donadieu

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6737)

Published: Feb. 27, 2025

Inferring cellular and molecular dynamics of multiple sclerosis (MS) lesions from postmortem tissue collected decades after onset is challenging. Using magnetic resonance image (MRI)-guided spatiotemporal RNA profiling in marmoset experimental autoimmune encephalitis (EAE), we mapped lesion modeled perturbations relevant to MS. Five distinct microenvironments emerged, involving neuroglial responses, destruction repair, brain border regulation. Before demyelination, MRI identified a high ratio proton density-weighted signal T1 relaxation time, capturing early hypercellularity, elevated astrocytic ependymal senescence signals marked perivascular periventricular areas that later became demyelination hotspots. As expanded, concentric glial barriers formed, initially dominated by proliferating diversifying microglia oligodendrocyte precursors, replaced monocytes lymphocytes. We highlight SERPINE1+ astrocytes as signaling hub underlying both EAE

Language: Английский

Citations

2
Neurodegeneration and demyelination in multiple sclerosis DOI
Thomas Garton, Sachin P. Gadani, Alexander J. Gill

et al.

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

Citations

14
Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis DOI Creative Commons

J.Q. Alida Chen,

Dennis Wever, Niamh B. McNamara

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Introduction Remyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relation microglia activation activity MS. Methods We correlated regenerative (CD163 + ) inflammatory (iNOS with BCAS1 oligodendrocytes, subdivided into early-stage (<3 processes) late-stage (≥3 cells brain donors high or low remyelinating potential remyelinated lesions active ramified/amoeboid (non-foamy) foamy microglia. A cohort categorized efficiently (ERDs; n=25) (PRDs; n=17) was included, based on their proportion at autopsy. Results discussion hypothesized more CD163 oligodendrocytes non-foamy from ERDs iNOS fewer PRDs. For microglia, however, no differences were observed donor groups. In line our hypothesis, found INOS significantly increased PRDs compared to within lesions, detected comparison Although for did find vs Interestingly, a positive correlation identified presence oligodendrocytes. These findings suggest impaired maturation encountering may underlie deficits unsuccessful lesion

Language: Английский

Citations

1
Optimizing Xenium In Situ data utility by quality assessment and best-practice analysis workflows DOI Creative Commons
Sergio Marco Salas,

Louis B. Kuemmerle,

Christoffer Mattsson-Langseth

et al.

Nature Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The Xenium In Situ platform is a new spatial transcriptomics product commercialized by 10x Genomics, capable of mapping hundreds genes in situ at subcellular resolution. Given the multitude commercially available technologies, recommendations choice and analysis guidelines are increasingly important. Herein, we explore 25 datasets generated from multiple tissues species, comparing scalability, resolution, data quality, capacities limitations with eight other spatially resolved technologies commercial platforms. addition, benchmark performance open-source computational tools, when applied to datasets, tasks including preprocessing, cell segmentation, selection variable features domain identification. This study serves as an independent Xenium, provides best practices for such datasets.

Language: Английский

Citations

1
Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis DOI Creative Commons

Matija Zelic,

Anna S. Blazier,

Fabrizio Pontarelli

et al.

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation prominent in ALS, but the cell state dynamics pathways driving remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords identified altered glial states, including increased expression inflammatory activation markers. Many these signals converged on inflammation death regulator receptor-interacting protein kinase 1 (RIPK1) necroptotic pathway. In superoxide dismutase (SOD1)G93A mice, blocking RIPK1 activity delayed symptom onset impairment modulated responses. used human induced pluripotent stem (iPSC)-derived neuron, astrocyte, microglia tri-cultures to identify potential biomarkers that are secreted upon vitro inhibition cerebrospinal fluid (CSF) people with ALS. These data reveal ALS-enriched populations associated suggest deleterious role for neuroinflammatory signaling pathogenesis.

Language: Английский

Citations

1
Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis DOI
Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema

et al.

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

Published: Nov. 5, 2024

Language: Английский

Citations

6
Spatial transcriptomic clocks reveal cell proximity effects in brain ageing DOI Creative Commons
Eric Sun, Olivia Y. Zhou, Max Hauptschein

et al.

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

Published: Dec. 18, 2024

Old age is associated with a decline in cognitive function and an increase neurodegenerative disease risk1. Brain ageing complex accompanied by many cellular changes2. Furthermore, the influence that aged cells have on neighbouring how this contributes to tissue unknown. More generally, tools systematically address question tissues not yet been developed. Here we generate spatially resolved single-cell transcriptomics brain atlas of 4.2 million from 20 distinct ages across adult lifespan two rejuvenating interventions—exercise partial reprogramming. We build spatial clocks, machine learning models trained atlas, identify cell-type-specific transcriptomic fingerprints ageing, rejuvenation disease, including for rare cell types. Using clocks deep learning, find T cells, which increasingly infiltrate age, marked pro-ageing proximity effect cells. Surprisingly, neural stem strong pro-rejuvenating also potential mediators their neighbours. These results suggest types can potent neighbours could be targeted counter ageing. Spatial represent useful tool studying cell–cell interactions contexts should allow scalable assessment efficacy interventions disease. A map mouse at different reveals signatures effects

Language: Английский

Citations

5
A practical guide to spatial transcriptomics DOI
Lukás Valihrach, Daniel Žucha, Pavel Abaffy

et al.

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101276 - 101276

Published: May 21, 2024

Language: Английский

Citations

4
Spatial Transcriptomics: Biotechnologies, Computational Tools, and Neuroscience Applications DOI Open Access
Qianwen Wang,

Hong-Yuan Zhu,

Linhong Deng

et al.

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Spatial transcriptomics (ST) represents a revolutionary approach in molecular biology, providing unprecedented insights into the spatial organization of gene expression within tissues. This review aims to elucidate advancements ST technologies, their computational tools, and pivotal applications neuroscience. It is begun with historical overview, tracing evolution from early image-based techniques contemporary sequence-based methods. Subsequently, methods essential for data analysis, including preprocessing, cell type annotation, clustering, detection spatially variable genes, cell-cell interaction 3D multi-slices integration are discussed. The central focus this application neuroscience, where it has significantly contributed understanding brain's complexity. Through ST, researchers advance brain atlas projects, gain development, explore neuroimmune dysfunctions, particularly tumors. Additionally, enhances neuronal vulnerability neurodegenerative diseases like Alzheimer's neuropsychiatric disorders such as schizophrenia. In conclusion, while already profoundly impacted challenges remain issues enhancing sequencing technologies developing robust tools. underscores transformative potential paving way new therapeutic research.

Language: Английский

Citations

0