Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1777 - 1792.e21

Published: May 1, 2022

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view current methodologies precludes their systematic application analyze relatively large three-dimensional mid- late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays in situ RNA capture create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq generate mouse organogenesis spatiotemporal atlas (MOSTA), which maps with single-cell high sensitivity kinetics directionality transcriptional variation during organogenesis. used this information gain insight into molecular basis cell heterogeneity fate specification developing tissues dorsal midbrain. Our panoramic will facilitate in-depth investigation longstanding questions concerning normal abnormal development.

Language: Английский

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Best practices for single-cell analysis across modalities

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 550 - 572

Published: March 31, 2023

Language: Английский

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An atlas of healthy and injured cell states and niches in the human kidney

Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 585 - 594

Published: July 19, 2023

Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell single-nucleus assays (>400,000 nuclei or cells) spatial imaging technologies to a broad spectrum healthy reference kidneys (45 donors) diseased (48 patients). This has provided high-resolution cellular atlas 51 main types, which include rare previously undescribed populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors localizations spanning entire kidney. We also define 28 states across nephron segments interstitium that were altered in injury, encompassing cycling, adaptive (successful maladaptive repair), transitioning degenerative states. Molecular signatures permitted localization these injury using transcriptomics, while large-scale 3D analysis (around 1.2 million neighbourhoods) corresponding linkages active immune responses. These analyses defined biological pathways are relevant time-course niches, including underlying epithelial repair predicted with decline function. integrated multimodal human represents comprehensive benchmark neighbourhoods, outcome-associated publicly available interactive visualizations.

Language: Английский

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Autism genes converge on asynchronous development of shared neuron classes

Nature, Journal Year: 2022, Volume and Issue: 602(7896), P. 268 - 273

Published: Feb. 2, 2022

Language: Английский

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SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks

Nature Methods, Journal Year: 2023, Volume and Issue: 20(9), P. 1355 - 1367

Published: July 13, 2023

Abstract Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven regulatory networks (GRNs). Here we present a method for the inference GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TFs) links these target genes. To improve both recall precision TF identification, curated clustered motif collection more than 30,000 motifs. We benchmarked on diverse datasets from different species, including human peripheral blood mononuclear cells, ENCODE cell lines, melanoma states Drosophila retinal development. Next, exploit predictions study conserved TFs, GRNs between mouse types cerebral cortex. Finally, use dynamics regulation differentiation trajectories effect perturbations state. is available at scenicplus.readthedocs.io .

Language: Английский

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hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data

Cell Reports Methods, Journal Year: 2023, Volume and Issue: 3(6), P. 100498 - 100498

Published: June 1, 2023

Biological systems are immensely complex, organized into a multi-scale hierarchy of functional units based on tightly regulated interactions between distinct molecules, cells, organs, and organisms. While experimental methods enable transcriptome-wide measurements across millions popular bioinformatic tools do not support systems-level analysis. Here we present hdWGCNA, comprehensive framework for analyzing co-expression networks in high-dimensional transcriptomics data such as single-cell spatial RNA sequencing (RNA-seq). hdWGCNA provides functions network inference, gene module identification, enrichment analysis, statistical tests, visualization. Beyond conventional RNA-seq, is capable performing isoform-level analysis using long-read data. We showcase from autism spectrum disorder Alzheimer's disease brain samples, identifying disease-relevant modules. directly compatible with Seurat, widely used R package demonstrate the scalability by dataset containing nearly 1 million cells.

Language: Английский

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Spatial epigenome–transcriptome co-profiling of mammalian tissues

Nature, Journal Year: 2023, Volume and Issue: 616(7955), P. 113 - 122

Published: March 15, 2023

Abstract Emerging spatial technologies, including transcriptomics and epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context 1–5 . However, current methods capture only one layer omics information at a time, precluding possibility examining mechanistic relationship across central dogma molecular biology. Here, we present two technologies spatially resolved, genome-wide, joint epigenome transcriptome by cosequencing chromatin accessibility gene expression, or histone modifications (H3K27me3, H3K27ac H3K4me3) expression on same section near-single-cell resolution. These were applied to embryonic juvenile mouse brain, as well adult human map how epigenetic mechanisms control transcriptional phenotype cell dynamics tissue. Although highly concordant features identified either also observed distinct patterns, suggesting their differential roles defining states. Linking pixel allows uncovering new insights priming, differentiation regulation within architecture. great interest life science biomedical research.

Language: Английский

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Universal DNA methylation age across mammalian tissues

Nature Aging, Journal Year: 2023, Volume and Issue: 3(9), P. 1144 - 1166

Published: Aug. 10, 2023

Abstract Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation pan-tissue epigenetic clocks. Here, we demonstrate development universal pan-mammalian clocks, 11,754 arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate age with high accuracy ( r > 0.96). Age deviations correlate human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines levels that change numerous sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated development, cancer, obesity longevity. Our findings offer new evidence suggesting aging is evolutionarily conserved intertwined developmental processes all mammals.

Language: Английский

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Gene regulatory network inference in the era of single-cell multi-omics

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(11), P. 739 - 754

Published: June 26, 2023

Language: Английский

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Inferring and perturbing cell fate regulomes in human brain organoids

Nature, Journal Year: 2022, Volume and Issue: 621(7978), P. 365 - 372

Published: Oct. 5, 2022

Self-organizing neural organoids grown from pluripotent stem cells

Language: Английский

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