Cell Type-Agnostic Transcriptomic Signatures Enable Uniform Comparisons of Neurodevelopment

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Single-cell transcriptomics has revolutionized our understanding of neurodevelopmental cell identities, yet, predicting a type's developmental state from its transcriptome remains challenge. We perform meta-analysis developing human brain datasets comprising over 2.8 million cells, identifying both tissue-level and cell-autonomous predictors age. While tissue composition predicts age within individual studies, it fails to generalize, whereas specific type proportions reliably track time across datasets. Training regularized regression models infer maturation, we find that type-agnostic model achieves the highest accuracy (error = 2.6 weeks), robustly capturing dynamics diverse types This generalizes neural organoids, accurately normal trajectories (R 0.91) disease-induced shifts in vitro . Furthermore, extends mouse brain, revealing an accelerated tempo relative humans. Our work provides unified framework for comparing neurodevelopment contexts, systems, species.

Language: Английский

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Polygenic enrichment analysis in multi-omics levels identifies cell/tissue specific associations with schizophrenia based on single-cell RNA sequencing data

Schizophrenia Research, Journal Year: 2025, Volume and Issue: 277, P. 93 - 101

Published: March 1, 2025

Language: Английский

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Thanks to new technologies, neuroscientists have more direct access to the human brain than ever before

The Transmitter, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Epigenetic and metabolic regulation of developmental timing in neocortex evolution

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The human brain is characterized by impressive cognitive abilities. neocortex the seat of higher cognition, and expansion a hallmark evolution. While developmental programs are similar in different species, timing transitions capacity neural progenitor cells (NPCs) to proliferate differ, contributing increased production neurons during cortical development. Here, we review epigenetic regulation corticogenesis, focusing mostly on humans while building knowledge from studies mice. We discuss metabolic-epigenetic interplay as potential mechanism integrate extracellular signals into chromatin. Moreover, synthesize current understanding how metabolic deregulation can cause neurodevelopmental disorders. Finally, outline be investigated using organoid models.

Language: Английский

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Cytoskeletal alterations in neuronal cells implicate Toxoplasma gondii secretory machinery and host microRNA-containing extracellular vesicles

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

The widespread protozoan Toxoplasma gondii chronically infects neural tissue in vertebrates and is linked to various neurological neuropsychiatric disorders humans. However, its effects on sparsely infected neurons broader circuits remain elusive. Our study reveals that T. infection disrupts cytoskeletal dynamics SH-SY5Y neuronal cells primary cortical neurons. Infected undergo significant cytomorphological changes, including retraction of dendritic extensions alterations microtubule F-actin networks, across both parasite genotypes I II. These were notably diminished exposed mutants with impaired secretion via the MYR translocon, independent intraneuronal replication. Moreover, a bystander effect was observed, supernatants from gondii-challenged inducing similar changes uninfected cells. Analyses extracellular vesicles (EVs) revealed differential expression host microRNAs response infection, most upregulation miR-221-3p, microRNA not previously associated gondii. data indicate unidentified parasite-derived effector(s) secreted conjunction MYR-independently induced EV-associated microRNAs, mediate findings provide new insights into molecular mechanisms by which may disrupt shedding light potential role dysregulation.

Language: Английский

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The amygdala and its networks

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Decoding human brain evolution: Insights from genomics

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103033 - 103033

Published: May 6, 2025

The human brain has undergone remarkable structural and functional specializations compared to that of nonhuman primates (NHPs), underlying the advanced cognitive abilities unique humans. However, cellular genetic basis driving these remains largely unknown. Comparing humans our closest living relatives, chimpanzee other great apes, is essential for identifying truly human-specific features. Recent comparative studies with closely related NHPs at single-cell resolution using multimodal genomic profiling, assisted high-throughput screening have provided unprecedented insights into features their underpinnings. In this review, we synthesize current knowledge evolution molecular levels, emphasizing how changes shaped adaptations. We also discuss emerging opportunities presented by new technologies comprehensive atlases advancing understanding evolution.

Language: Английский

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Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(5)

Published: May 1, 2025

Abstract INTRODUCTION In Alzheimer's disease (AD), fibrillar tau gradually progresses from initial seed to larger brain area. However, those properties underlying the region‐dependent susceptibility accumulation remain unclear. METHODS We constructed multimodal spatial gradients characterize molecular and connectomic architecture. A predictive model for regional deposition was developed by integrating embeddings in principal of global connectome with gene expression, neurotransmitters, myelin, amyloid‐beta. The trained on amyloid‐beta–positive participants Disease Neuroimaging Initiative (ADNI) externally validated independent datasets. RESULTS combination explained up 77.7% cross‐sectional 77.3% longitudinal inter‐regional variance deposition. Gene set enrichment analysis a major expression gradient points synaptic transmission confer increased tau. DISCUSSION Our findings reveal spatially heterogeneous landscape shaping deposition, presenting powerful system‐level explanatory pathology AD. Highlights Spatial fundamental associated pathology. power showed high consistency across studies. Genetic analyses suggested that synapse plays vital role accumulation.

Language: Английский

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Unraveling the Interplay Between Metabolism and Neurodevelopment in Health and Disease

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(5)

Published: May 1, 2025

ABSTRACT Background Neurodevelopment is a multifaceted and tightly regulated process essential for the formation, maturation, functional specialization of nervous system. It spans critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, synaptic pruning, which collectively establish foundation cognitive, behavioral, emotional functions. Metabolism serves as cornerstone neurodevelopment, providing energy substrates necessary biosynthesis, signaling, activities. Results Key metabolic pathways, glycolysis, lipid metabolism, amino acid support processes such cell myelination, neurotransmitter synthesis. Crucial signaling insulin, mTOR, AMPK, further regulate neuronal growth, plasticity, homeostasis. Dysregulation these linked to spectrum neurodevelopmental disorders, autism disorders (ASDs), intellectual disabilities, epilepsy. Conclusions This review investigates intricate interplay between elucidating molecular mechanisms that govern brain development pathogenesis disorders. Additionally, it highlights potential avenues innovative strategies aimed at enhancing health function.

Language: Английский

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Consciousness makes sense in the light of evolution

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 164, P. 105824 - 105824

Published: July 22, 2024

I believe consciousness is a property of advanced nervous systems, and as such product evolution. Thus, to understand we need describe the trajectory leading its evolution selective advantages conferred. A deeper understanding neurology would be significant contribution, but other functions, hearing vision, are explained with comparable lack detailed knowledge brain processes responsible. In this paper, try add details credence previously suggested, evolution-based model consciousness. According model, feature started evolve in early amniotes (reptiles, birds, mammals) some 320 million years ago. The reason was introduction feelings strategy for making behavioral decisions.

Language: Английский

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