Unsupervised spatially embedded deep representation of spatial transcriptomics

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 12, 2024

Abstract Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting to dissect tissue heterogeneity map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with masked self-supervised learning mechanism construct low-dimensional latent representation gene expression, then simultaneously embedded the corresponding through variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets better scalability high-resolution than existing methods. Additionally, we show SEDR’s ability impute denoise expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).

Language: Английский

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Towards a youth mental health paradigm: a perspective and roadmap

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3171 - 3181

Published: Aug. 1, 2023

Abstract Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance this period for pathogenesis, diagnosis, treatment ill-health. This perspective addresses interactions risk protective factors brain development as key pillars accounting emergence psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis interventions are required reflect evolution emerging psychopathology, service models, knowledge exchange science practitioners. Taken together, transformative intervention paradigm research clinical care could significantly enhance health young people initiate shift prevention severe disorders.

Language: Английский

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An increase of inhibition drives the developmental decorrelation of neural activity

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 17, 2022

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as latter is thought allow for more efficient storage, retrieval, processing of information. Here, we show that, in mouse medial prefrontal cortex (mPFC), during first two postnatal weeks decorrelates following specific spatial patterns. This accompanied by concomitant tilting excitation-inhibition (E-I) ratio toward inhibition. Using optogenetic manipulations network modeling, that phenomena mechanistically linked, relative increase inhibition drives decorrelation activity. Accordingly, mice mimicking etiology neurodevelopmental disorders, subtle alterations E-I associated impairments correlational structure spike trains. Finally, capitalizing on EEG data newborn babies, an analogous takes place also human brain. Thus, changes control (de)correlation and, these means, its imbalance might contribute pathogenesis disorders.

Language: Английский

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Adolescence is a sensitive period for prefrontal microglia to act on cognitive development

Science Advances, Journal Year: 2022, Volume and Issue: 8(9)

Published: March 2, 2022

The prefrontal cortex (PFC) is a cortical brain region that regulates various cognitive functions. One distinctive feature of the PFC its protracted adolescent maturation, which necessary for acquiring mature abilities in adulthood. Here, we show microglia, brain's resident immune cells, contribute to this maturational process. We find transient and cell-specific deficiency microglia adolescence sufficient induce an adult emergence PFC-associated impairments functions, dendritic complexity, synaptic structures. While also altered excitatory-inhibitory balance circuits, there were no sequelae when depleted Thus, our findings identify as sensitive period act on development.

Language: Английский

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The gut microbiome modulates the transformation of microglial subtypes

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(4), P. 1611 - 1621

Published: March 13, 2023

Abstract Clinical and animal studies have shown that gut microbiome disturbances can affect neural function behaviors via the microbiota–gut–brain axis, may be implicated in pathogenesis of several brain diseases. However, exactly how modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize cell type–specific transcriptomic changes prefrontal cortex hippocampus derived from germ-free (GF), specific pathogen free, colonized-GF mice. We found absence microbiota resulted cell-specific changes. Furthermore, microglia transcriptomes were preferentially influenced, which could effectively reversed by microbial colonization. Significantly, modulated mutual transformation microglial subpopulations two regions. Cross-species analysis showed transcriptome these mainly associated with Alzheimer’s disease (AD) major depressive disorder (MDD), further supported behavioral tests. Our findings demonstrate modulate subtypes, lead new insights into AD MDD.

Language: Английский

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Precision drug delivery to the central nervous system using engineered nanoparticles

Nature Reviews Materials, Journal Year: 2024, Volume and Issue: 9(8), P. 567 - 588

Published: June 25, 2024

Language: Английский

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Neural interfaces: Bridging the brain to the world beyond healthcare

Exploration, Journal Year: 2024, Volume and Issue: 4(5)

Published: March 14, 2024

Abstract Neural interfaces, emerging at the intersection of neurotechnology and urban planning, promise to transform how we interact with our surroundings communicate. By recording decoding neural signals, these interfaces facilitate direct connections between brain external devices, enabling seamless information exchange shared experiences. Nevertheless, their development is challenged by complexities in materials science, electrochemistry, algorithmic design. Electrophysiological crosstalk mismatch electrode rigidity tissue flexibility further complicate signal fidelity biocompatibility. Recent closed‐loop brain‐computer while promising for mood regulation cognitive enhancement, are limited accuracy adaptability user interfaces. This perspective outlines challenges discusses progress contrasting non‐invasive invasive approaches, explores dynamics stimulation interfacing. Emphasis placed on applications beyond healthcare, highlighting need implantable high‐resolution capabilities.

Language: Английский

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Impact of Early Life Stress on Reward Circuit Function and Regulation

Frontiers in Psychiatry, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 20, 2021

Early life stress – including experience of child maltreatment, neglect, separation from or loss a parent, and other forms adversity increases lifetime risk mood, anxiety, substance use disorders. A major component this may be early stress-induced alterations in motivation reward processing, mediated by changes the nucleus accumbens (NAc) ventral tegmental area (VTA). Here, we review evidence impact on circuit structure function human animal models, with focus NAc. We then connect these results to emerging theoretical models about indirect direct impacts development. Through synthesis, aim highlight open research questions suggest avenues future study service basic science, as well applied insights. Understanding how alters development, function, motivated behaviors is critical first step toward developing ability predict, prevent, treat stress-related psychopathology spanning

Language: Английский

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A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice

Neuron, Journal Year: 2021, Volume and Issue: 109(8), P. 1350 - 1364.e6

Published: March 7, 2021

Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold dysfunction by interfering with apoptosis, dendritic growth, synapse formation. However, how altered electrical early life affects function behavior adults is unknown. Here, we address this question transiently increasing the coordinated of layer 2/3 pyramidal neurons medial prefrontal cortex neonatal mice monitoring long-term functional behavioral consequences. We show that increased causes premature maturation interneuronal density. Consequently, inhibitory feedback fast-spiking interneurons excitation/inhibition imbalance circuits young result weaker evoked synchronization gamma frequency. These structural changes ultimately lead to poorer mnemonic social abilities. Thus, actively controls cognitive performance be critical for symptoms diseases.

Language: Английский

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Unsupervised Spatially Embedded Deep Representation of Spatial Transcriptomics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: June 16, 2021

Abstract Spatial transcriptomics enable us to dissect tissue heterogeneity and map out inter-cellular communications. Optimal integration of data associated spatial information is essential towards fully exploiting the data. We present SEDR, an unsupervised spatially embedded deep representation both transcript information. The SEDR pipeline uses a autoencoder construct low-dimensional latent gene expression, which then simultaneously with corresponding through variational graph autoencoder. applied on human dorsolateral prefrontal cortex achieved better clustering accuracy, correctly retraced prenatal development order trajectory analysis. also found be eminently suited for batch integration. Applying breast cancer data, we discerned heterogeneous sub-regions within visually homogenous tumor region, identifying core pro-inflammatory microenvironment outer ring region enriched macrophages drives immune suppressive microenvironment.

Language: Английский

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