Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease DOI Creative Commons
Lyandysha V. Zholudeva, Victoria E. Abraira, Kajana Satkunendrarajah

et al.

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(5), P. 845 - 854

Published: Jan. 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.

Language: Английский

Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results DOI
Sergio Crespo‐Garcia, Frédérik Fournier, Roberto Diaz-Marin

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(2), P. 443 - 454

Published: Feb. 1, 2024

Language: Английский

Citations

37

The future of rapid and automated single-cell data analysis using reference mapping DOI Creative Commons
Mohammad Lotfollahi, Yuhan Hao, Fabian J. Theis

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(10), P. 2343 - 2358

Published: May 1, 2024

As the number of single-cell datasets continues to grow rapidly, workflows that map new data well-curated reference atlases offer enormous promise for biological community. In this perspective, we discuss key computational challenges and opportunities reference-mapping algorithms. We how mapping algorithms will enable integration diverse across disease states, molecular modalities, genetic perturbations, species eventually replace manual laborious unsupervised clustering pipelines.

Language: Английский

Citations

27

Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica DOI
Michael A. Skinnider, Matthieu Gautier, Yue Yang Teo

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 150 - 163

Published: June 19, 2024

Language: Английский

Citations

26

Cell-type-specific effects of age and sex on human cortical neurons DOI Creative Commons
Jo-fan Chien, Hanqing Liu, Bang-An Wang

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(15), P. 2524 - 2539.e5

Published: June 5, 2024

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation transcriptome sequencing (snmCT-seq) in frontal cortex from young adult aged donors, we found widespread age- sex-related variation specific neuron types. The proportion inhibitory SST- VIP-expressing neurons was reduced donors. Excitatory had more profound age-related their gene expression than cells. Hundreds genes involved synaptic activity, including EGR1, were less expressed adults. Genes located subtelomeric regions increased age correlated telomere length. We further mapped cell-type-specific sex differences X-inactivation escape genes. Multi-omic epigenomes transcriptomes provide new insight into the effects on human neurons.

Language: Английский

Citations

17

Brain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice DOI Creative Commons
Kelly Jin, Zizhen Yao, Cindy T. J. van Velthoven

et al.

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

Published: Jan. 1, 2025

Biological ageing can be defined as a gradual loss of homeostasis across various aspects molecular and cellular function1,2. Mammalian brains consist thousands cell types3, which may differentially susceptible or resilient to ageing. Here we present comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality transcriptomes brain cells from young adult aged mice both sexes, regions spanning the forebrain, midbrain hindbrain. High-resolution clustering all results in 847 clusters reveals at least 14 age-biased that are mostly glial types. At broader subclass supertype levels, find age-associated gene expression signatures provide list 2,449 unique expressed genes (age-DE genes) for many neuronal non-neuronal Whereas most age-DE specific types, observe common with including decrease related structure function neuron major astrocyte types mature oligodendrocytes, an increase immune function, antigen presentation, inflammation, motility some vascular Finally, demonstrate greatest sensitivity concentrated around third ventricle hypothalamus, tanycytes, ependymal cells, certain arcuate nucleus, dorsomedial nucleus paraventricular express canonically energy homeostasis. Many these response. These findings suggest hypothalamus hub mouse brain. Overall, this study systematically delineates dynamic landscape cell-type-specific transcriptomic changes associated normal will serve foundation investigation functional interaction disease. A inform into

Language: Английский

Citations

7

Analysis of multi-condition single-cell data with latent embedding multivariate regression DOI Creative Commons
Constantin Ahlmann-Eltze, Wolfgang Huber

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

Published: Jan. 3, 2025

Abstract Identifying gene expression differences in heterogeneous tissues across conditions is a fundamental biological task, enabled by multi-condition single-cell RNA sequencing (RNA-seq). Current data analysis approaches divide the constituent cells into clusters meant to represent cell types, but such discrete categorization tends be an unsatisfactory model of underlying biology. Here, we introduce latent embedding multivariate regression (LEMUR), that operates without, or before, commitment categorization. LEMUR (1) integrates from different conditions, (2) predicts each cell’s changes as function and its position space (3) for gene, identifies compact neighborhood with consistent differential expression. We apply cancer, zebrafish development spatial gradients Alzheimer’s disease, demonstrating broad applicability.

Language: Английский

Citations

2

Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer DOI Creative Commons
Jian Zhang, Tony Pan, Jimmy Lee

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101920 - 101920

Published: Jan. 1, 2025

Metabolic reprogramming of tumor cells is an emerging hallmark cancer. Among all the changes in cancer metabolism, increased glucose uptake and accumulation lactate under normoxic conditions (the "Warburg effect") a common feature cells. In this study, we develop lactate-responsive drug delivery platform by targeting Warburg effect. We design test gold/mesoporous silica Janus nanoparticle system as gated carrier, which gold particles are functionalized with oxidase capped α-cyclodextrin through surface arylboronate modification. presence lactate, generates hydrogen peroxide, induces self-immolation reaction arylboronate, leading to uncapping release. Our results demonstrate greatly improved specificity therapeutic efficacy for treatment different cancers. findings present effective approach metabolic tumors.

Language: Английский

Citations

2

Single-cell delineation of the microbiota-gut-brain axis: Probiotic intervention in Chd8 haploinsufficient mice DOI Creative Commons
Peifeng Ji, Ning Wang,

You Yu

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100768 - 100768

Published: Feb. 1, 2025

Emerging research underscores the gut microbiome's impact on nervous system via microbiota-gut-brain axis, yet comprehensive insights remain limited. Using a CHD8-haploinsufficient model for autism spectrum disorder (ASD), we explored host-gut microbiota interactions by constructing single-cell transcriptome atlas of brain and intestinal tissues in wild-type mutant mice across three developmental stages. CHD8 haploinsufficiency caused delayed development radial glial precursors excitatory neural progenitors E14.5 brain, inflammation adult immunodeficiency, abnormal development. Selective knockdown epithelial cells generated Chd8ΔIEC mice, which exhibited normal sociability but impaired social novelty recognition. Probiotic intervention with Lactobacillus murinus selectively rescued deficits analysis revealing underlying mechanisms. This study provides detailed transcriptomic dataset ASD-related changes, advancing our understanding gut-brain axis offering potential therapeutic strategies ASD.

Language: Английский

Citations

2

Sensory input, sex and function shape hypothalamic cell type development DOI Creative Commons
Harris S. Kaplan, Brandon L. Logeman, Kai Zhang

et al.

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

Published: March 5, 2025

Language: Английский

Citations

2

GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice DOI Creative Commons
Robert M. Gutgesell, Ahmed Khalil, Arkadiusz Liśkiewicz

et al.

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

Published: April 29, 2025

Language: Английский

Citations

2