Organizational principles of the primate cerebral cortex at the single-cell level DOI
Renrui Chen, Pengxing Nie, Liangxiao Ma

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 7, 2024

Abstract The primate cerebral cortex, the major organ for cognition, consists of an immense number neurons. However, organizational principles governing these neurons remain unclear. By accessing single-cell spatial transcriptome over 25 million neuron cells across entire macaque we discovered that distribution within cortical layers is highly non-random. Strikingly, three-quarters are located in distinct neuronal clusters. Within clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory clusters mainly consist excitatory-excitatory combinations, while inhibitory primarily contain excitatory-inhibitory combinations. Both cluster have roughly equal numbers each layer. Importantly, most and form partnerships, indicating a balanced local network correlating with specific functional regions. These findings suggest brain regions cortex may exhibit similar mechanisms at population level.

Язык: Английский

Single-cell genomics and regulatory networks for 388 human brains DOI
Prashant S. Emani, Jason Liu, Declan Clarke

и другие.

Science, Год журнала: 2024, Номер 384(6698)

Опубликована: Май 23, 2024

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into resource comprising >2.8 million nuclei from prefrontal cortex across 388 individuals. For 28 cell types, assessed population-level variation in expression and chromatin families drug targets. We identified >550,000 type-specific regulatory elements >1.4 single-cell quantitative trait loci, which used to build cell-type cell-to-cell communication networks. These networks manifest cellular changes aging neuropsychiatric disorders. further constructed an integrative model accurately imputing simulating perturbations; prioritized ~250 disease-risk genes targets with associated types.

Язык: Английский

Процитировано

38
Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood DOI
Nikolaos P. Daskalakis, Artemis Iatrou, Chris Chatzinakos

и другие.

Science, Год журнала: 2024, Номер 384(6698)

Опубликована: Май 23, 2024

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided underlying genomic structure. Single RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) non-neuronal cell types. Analyses brain-blood intersections >50,000 UK Biobank participants were conducted along with fine-mapping results PTSD MDD genome-wide association studies distinguish risk from processes. data suggest shared distinct both propose potential therapeutic targets biomarkers.

Язык: Английский

Процитировано

21
Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation DOI Creative Commons
Anthony D. Ramnauth, Madhavi Tippani, Heena R. Divecha

и другие.

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115300 - 115300

Опубликована: Фев. 1, 2025

The dentate gyrus of the hippocampus is important for many cognitive functions, including learning, memory, and mood. Here, we present transcriptome-wide spatial gene expression maps human investigate age-associated changes across lifespan. Genes associated with neurogenesis extracellular matrix are enriched in infants decline throughout development maturation. Following infancy, inhibitory neuron markers increase, cellular proliferation decrease. We also identify spatio-molecular signatures that support existing evidence protracted maturation granule cells during adulthood increases neuroinflammation-related expression. Our findings notion hippocampal neurogenic niche undergoes major following infancy molecular regulators brain aging glial- neuropil-enriched tissue.

Язык: Английский

Процитировано

1
White matter damage and degeneration in traumatic brain injury DOI Creative Commons
Regina C. Armstrong, Genevieve M. Sullivan, Daniel P. Perl

и другие.

Trends in Neurosciences, Год журнала: 2024, Номер 47(9), С. 677 - 692

Опубликована: Авг. 10, 2024

Traumatic brain injury (TBI) is a complex condition that can resolve over time but all too often leads to persistent symptoms, and the risk of poor patient outcomes increases with aging. TBI damages neurons long axons within white matter tracts are critical for communication between regions; this causes slowed information processing neuronal circuit dysfunction. This review focuses on after multifactorial processes underlie damage, potential recovery, progression degeneration. A multiscale perspective across clinical preclinical advances presented encourage interdisciplinary insights from whole-brain neuroimaging down cellular molecular responses axons, myelin, glial cells tissue.

Язык: Английский

Процитировано

5
Stereo-seq of the prefrontal cortex in aging and Alzheimer’s disease DOI Creative Commons

Yun Gong,

Mohammad Haeri, Xiao Zhang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 8, 2025

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in prefrontal cortex (PFC). We present first subcellular-resolution spatial transcriptome atlas of human (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages age-matched controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions laminar structure, exposed AD-related shifts layer-to-layer cell-cell interactions. Notably, we identified genes highly upregulated stressed neurons nearby glial cells, where diminished stress-response interactions that promote Aβ clearance. Further, cell-type-specific co-expression analysis three neuronal modules linked to neuroprotection, protein dephosphorylation, regulation, all downregulated as progresses. ZNF460 a transcription factor regulating these modules, offering potential therapeutic target. In summary, this provides valuable insight into AD's molecular mechanisms. (AD). Here, authors AD, revealing alterations.

Язык: Английский

Процитировано

0
Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder DOI
Anna S. Warden, Nihal A. Salem, Eric Brenner

и другие.

Biological Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex DOI Creative Commons
Louise A. Huuki-Myers, Kelsey D. Montgomery, Sang Ho Kwon

и другие.

Genome biology, Год журнала: 2025, Номер 26(1)

Опубликована: Апрель 7, 2025

Язык: Английский

Процитировано

0
Spatial Transcriptomics: Biotechnologies, Computational Tools, and Neuroscience Applications DOI Open Access
Qianwen Wang,

Hong-Yuan Zhu,

Linhong Deng

и другие.

Small Methods, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

Процитировано

0
Organizational Principles of the Primate Cerebral Cortex at the Single‐Cell Level DOI Creative Commons
Renrui Chen, Pengxing Nie, Liangxiao Ma

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract The primate cerebral cortex, the major organ for cognition, consists of an immense number neurons. However, organizational principles governing these neurons remain unclear. By accessing single‐cell spatial transcriptome over 25 million neuron cells across entire macaque it is discovered that distribution within cortical layers highly non‐random. Strikingly, three‐quarters are located in distinct neuronal clusters. Within clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory clusters mainly consist excitatory‐excitatory combinations, while inhibitory primarily contain excitatory‐inhibitory combinations. Both cluster have roughly equal numbers each layer. Importantly, most and form partnerships, indicating a balanced local network correlating with specific functional regions. These conserved mouse findings suggest brain regions cortex may exhibit similar mechanisms at population level.

Язык: Английский

Процитировано

0
Spatial and single-nucleus transcriptomic profile of a chimpanzee frontal pole DOI Creative Commons
Gökberk Alagöz, Maggie Wong, Tobias Gräßle

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Abstract Chimpanzees, our closest living relatives, share a vast amount of genetic code, with the majority differences found in non-coding regions genome. Functional and gene regulatory drive phenotypic divergence, including distinctive brain anatomy humans compared to chimpanzees other apes. However, little is known about species expression, how they relate evolution neuroanatomy cognition. This primarily due limited availability great ape samples challenges comparative spatial transcriptomic studies. Here, we present first data from chimpanzee based on post mortem tissue an adult female, who was euthanised poor health. We focus frontal pole, region that has undergone significant evolutionary changes size organisation since last common ancestor chimpanzees, considered critical for cognitive evolution. examined expression profiles cell-type composition pole left hemisphere, both neuronal non-neuronal cell types across cortical layers white matter. By integrating publicly available single-nucleus dataset dorsolateral prefrontal cortex, mapped distribution 29 types. study represents step towards characterisation between brains non-human apes humans.

Язык: Английский

Процитировано

0