Deciphering brain cellular and behavioral mechanisms: Insights from single‐cell and spatial RNA sequencing DOI
Renrui Chen, Pengxing Nie, Jing Wang

и другие.

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2024, Номер 15(4)

Опубликована: Июль 1, 2024

The brain is a complex computing system composed of multitude interacting neurons. computational outputs this determine the behavior and perception every individual. Each cell expresses thousands genes that dictate cell's function physiological properties. Therefore, deciphering molecular expression each great significance for understanding its characteristics role in function. Additionally, positional information can provide crucial insights into their involvement local circuits. In review, we briefly overview principles single-cell RNA sequencing spatial transcriptomics, potential issues challenges data processing, applications research. We further outline several promising directions neuroscience could be integrated with sequencing, including neurodevelopment, identification novel microstructures, cognition behavior, neuronal positioning, molecules cells related to advanced functions, sleep-wake cycles/circadian rhythms, modeling believe deep integration these contribute significantly roles individual or types specific thereby making important contributions addressing critical questions those fields. This article categorized under: Evolution Genomics > Computational Analyses Disease Development Disease.

Язык: Английский

Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain DOI Creative Commons
Hanqing Liu, Qiurui Zeng, Jingtian Zhou

и другие.

Nature, Год журнала: 2023, Номер 624(7991), С. 366 - 377

Опубликована: Дек. 13, 2023

Cytosine DNA methylation is essential in brain development and implicated various neurological disorders. Understanding diversity across the entire a spatial context fundamental for complete molecular atlas of cell types their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) multi-omic (snm3C-seq)

Язык: Английский

Процитировано

55
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium DOI
Nikolai Hecker, Niklas Kempynck, David Mauduit

и другие.

Science, Год журнала: 2025, Номер 387(6735)

Опубликована: Янв. 2, 2025

Combinations of transcription factors govern the identity cell types, which is reflected by genomic enhancer codes. We used deep learning to characterize these codes and devised three metrics compare types in telencephalon across amniotes. To this end, we generated single-cell multiome spatially resolved transcriptomics data chicken telencephalon. Enhancer orthologous nonneuronal γ-aminobutyric acid–mediated (GABAergic) show a high degree similarity amniotes, whereas excitatory neurons mammalian neocortex avian pallium exhibit varying degrees similarity. mesopallial are most similar those deep-layer neurons. With study, present generally applicable approaches on basis regulatory sequences.

Язык: Английский

Процитировано

2
A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types DOI Creative Commons
Yoav Ben‐Simon, Marcus Hooper, Sujatha Narayan

и другие.

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

Опубликована: Июнь 10, 2024

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different covering most subclasses cells. tools reported here as well scaled process tool creation modification enable diverse experimental strategies towards brain function.

Язык: Английский

Процитировано

11
Single-cell technology grows up: Leveraging high-resolution omics approaches to understand neurodevelopmental disorders DOI Creative Commons
Joseph D. Dougherty, Simona Sarafinovska, Sneha Chaturvedi

и другие.

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 102990 - 102990

Опубликована: Март 3, 2025

Язык: Английский

Процитировано

1
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium DOI Creative Commons
Nikolai Hecker, Niklas Kempynck, David Mauduit

и другие.

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

Опубликована: Апрель 18, 2024

Combinations of transcription factors govern the identity cell types, which is reflected by enhancer codes in cis-regulatory genomic regions. Cell type-specific at nucleotide-level resolution have not yet been characterized for mammalian neocortex. It currently unknown whether these are conserved other vertebrate brains, and they informative to resolve homology relationships species that lack a neocortex such as birds. To compare types from with those bird pallium, we generated single-cell multiome spatially-resolved transcriptomics data chicken telencephalon. We then trained deep learning models characterize human, mouse, devised three metrics exploit between species. Based on metrics, non-neuronal GABAergic show high degree regulatory similarity across vertebrates. Proposed homologies neocortical avian pallial excitatory neurons still debated. Our code based comparison shows pallium exhibit higher divergence than types. In contrast existing evolutionary models, layer most similar mesopallial neurons; upper hyper- nidopallial their codes. addition characterizing telencephalon, revealing unexpected correspondences present generally applicable approaches via code.

Язык: Английский

Процитировано

5
Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain DOI Creative Commons
Hanqing Liu, Qiurui Zeng, Jingtian Zhou

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 18, 2023

Cytosine DNA methylation is essential in brain development and has been implicated various neurological disorders. A comprehensive understanding of diversity across the entire context brain's 3D spatial organization for building a complete molecular atlas cell types their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) multi-omic (snm3C-seq

Язык: Английский

Процитировано

12
MYT1L deficiency impairs excitatory neuron trajectory during cortical development DOI Creative Commons
Allen Yen, Simona Sarafinovska,

Xuhua Chen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 27, 2024

Abstract Mutations reducing the function of MYT1L, a neuron-specific transcription factor, are associated with syndromic neurodevelopmental disorder. MYT1L is used as pro-neural factor in fibroblast-to-neuron transdifferentiation and hypothesized to influence neuronal specification maturation, but it not clear which neuron types most impacted by loss. In this study, we profile 412,132 nuclei from forebrains wild-type MYT1L-deficient mice at three developmental stages: E14 peak neurogenesis, P1 when cortical neurons have been born, P21 maturing, examine role levels on development. deficiency disrupts proportions gene expression, primarily affecting maturation programs. Effects mostly cell autonomous persistent through While can both activate repress repressive effects sensitive haploinsufficiency, likely mediating syndrome. These findings illuminate MYT1L’s orchestrating expression during development, providing insights into molecular underpinnings

Язык: Английский

Процитировано

4
Annotation of single-cell clusters using marker genes within and across species DOI

Sanchari Kundu,

Tran Chau,

Dena Saghai Maroof

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 321 - 347

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Chromatin accessibility provides a window into the genetic etiology of human brain disease DOI
Jaroslav Bendl, John F. Fullard, Kiran Girdhar

и другие.

Trends in Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
EpiFoundation: A Foundation Model for Single-Cell ATAC-seq via Peak-to-Gene Alignment DOI Creative Commons

Jun-Cheng Wu,

Changxin Wan, Zhicheng Ji

и другие.

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

Опубликована: Фев. 8, 2025

Abstract Foundation models exhibit strong capabilities for downstream tasks by learning generalized representations through self-supervised pre-training on large datasets. While several foundation have been developed single-cell RNA-seq (scRNA-seq) data, there is still a lack of specifically tailored ATAC-seq (scATAC-seq), which measures epigenetic information in individual cells. The principal challenge developing such model lies the vast number scATAC peaks and significant sparsity complicates formulation peak-to-peak correlations. To address this challenge, we introduce EpiFoundation , cell from high-dimensional sparse space peaks. Epi-Foundation relies an innovative cross-modality procedure with two key technical innovations. First, exclusively processes non-zero peak set, thereby enhancing density cell-specific within input data. Second, utilizes dense gene expression to supervise process, aligning peak-to-gene can handle various types tasks, including cell-type annotation, batch correction, prediction. train validate EpiFoundation, curated MiniAtlas dataset 100,000+ single cells paired scRNA-seq scATAC-seq along diverse test sets spanning tissues robust evaluation. demonstrates state-of-the-art performance across multiple tasks.

Язык: Английский

Процитировано

0