Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease DOI Creative Commons
Constanze Depp, Ting Sun, Andrew Octavian Sasmita

et al.

Nature, Journal Year: 2023, Volume and Issue: 618(7964), P. 349 - 357

Published: May 31, 2023

The incidence of Alzheimer's disease (AD), the leading cause dementia, increases rapidly with age, but why age constitutes main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and structural integrity myelin sheaths1, latter which associated secondary neuroinflammation2,3. As support axonal energy metabolism neuronal health4-7, we hypothesized that loss could be an upstream for amyloid-β (Aβ) deposition, central neuropathological hallmark AD. Here identify genetic pathways dysfunction demyelinating injuries as potent drivers amyloid deposition in mouse models Mechanistically, causes accumulation Aβ-producing machinery within swellings cleavage cortical precursor protein. Suprisingly, AD mice dysfunctional lack plaque-corralling microglia despite overall increase their numbers. Bulk single-cell transcriptomics defects show there a concomitant induction highly similar distinct disease-associated signatures specific to damage plaques, respectively. Despite successful induction, (DAM) usually clear plaques are apparently distracted nearby damage. Our data suggest working model whereby age-dependent promote Aβ plaque formation directly indirectly therefore factor. Improving oligodendrocyte health promising target delay development slow progression

Language: Английский

Reactive astrocyte nomenclature, definitions, and future directions DOI Open Access
Carole Escartin, Elena Galea, András Lakatos

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(3), P. 312 - 325

Published: Feb. 15, 2021

Language: Английский

Citations

1673

Exploring tissue architecture using spatial transcriptomics DOI
Anjali Rao, Dalia Barkley, Gustavo S. França

et al.

Nature, Journal Year: 2021, Volume and Issue: 596(7871), P. 211 - 220

Published: Aug. 11, 2021

Language: Английский

Citations

1069

Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics DOI
Sophia K. Longo, Margaret Guo, Andrew L. Ji

et al.

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(10), P. 627 - 644

Published: June 18, 2021

Language: Английский

Citations

672

Single‐cell RNA sequencing technologies and applications: A brief overview DOI

Dragomirka Jovic,

Xue Liang, Zeng Hua

et al.

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(3)

Published: March 1, 2022

Language: Английский

Citations

655

SpaGCN: Integrating gene expression, spatial location and histology to identify spatial domains and spatially variable genes by graph convolutional network DOI
Jian Hu, Xiangjie Li, Kyle Coleman

et al.

Nature Methods, Journal Year: 2021, Volume and Issue: 18(11), P. 1342 - 1351

Published: Oct. 28, 2021

Language: Английский

Citations

601

An introduction to spatial transcriptomics for biomedical research DOI Creative Commons

Cameron G. Williams,

Hyun Jae Lee,

Takahiro Asatsuma

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: June 27, 2022

Abstract Single-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact viable from tissue. This precluded many cell types study largely destroys spatial context that could otherwise inform analyses of identity function. An increasing number platforms now facilitate spatially resolved, high-dimensional assessment gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes method, which either record locations hybridized mRNA molecules tissue, image positions themselves prior assessment, or employ arrays probes pre-determined location. We review sizes tissue area can assessed, their resolution, genes profiled. discuss if preservation influences choice platform, provide guidance on whether specific may better suited discovery screens hypothesis testing. Finally, bioinformatic methods analysing transcriptomic data, including pre-processing, integration with existing inference cell-cell interactions. Spatial -omics are already improving our understanding human tissues research, diagnostic, therapeutic settings. To build upon these recent advancements, entry-level those seeking own research.

Language: Английский

Citations

462

Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease DOI
Kun Leng, Emmy Li, Rana Eser

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(2), P. 276 - 287

Published: Jan. 11, 2021

Language: Английский

Citations

348

White matter aging drives microglial diversity DOI Creative Commons
Shima Safaiyan, Simon Besson‐Girard, Tuğberk Kaya

et al.

Neuron, Journal Year: 2021, Volume and Issue: 109(7), P. 1100 - 1117.e10

Published: Feb. 19, 2021

Language: Английский

Citations

308

Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression DOI Creative Commons
Haixia Wang, Yi He, Zuoli Sun

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 6, 2022

Abstract Major depressive disorder is a highly debilitating psychiatric involving the dysfunction of different cell types in brain. Microglia are predominant resident immune cells brain and exhibit critical role depression. Recent studies have suggested that depression can be regarded as microglial disease. regulate inflammation, synaptic plasticity, formation neural networks, all which affect In this review, we highlighted microglia pathology First, described activation animal models clinically depressed patients. Second, emphasized possible mechanisms by recognize depression-associated stress conditions. Third, how antidepressants (clinical medicines natural products) activation. Thus, review aimed to objectively analyze focus on potential antidepressants. These data regulation actions might novel therapeutic strategy counteract adverse effects devastating mental disorders.

Language: Английский

Citations

292

The emerging landscape of spatial profiling technologies DOI
Jeffrey R. Moffitt, Emma Lundberg, Holger Heyn

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 741 - 759

Published: July 20, 2022

Language: Английский

Citations

277