Methods and applications for single-cell and spatial multi-omics

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 494 - 515

Published: March 2, 2023

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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The technological landscape and applications of single-cell multi-omics

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 695 - 713

Published: June 6, 2023

Language: Английский

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The dawn of spatial omics

Science, Journal Year: 2023, Volume and Issue: 381(6657)

Published: Aug. 3, 2023

Spatial omics has been widely heralded as the new frontier in life sciences. This term encompasses a wide range of techniques that promise to transform many areas biology and eventually revolutionize pathology by measuring physical tissue structure molecular characteristics at same time. Although field came age past 5 years, it still suffers from some growing pains: barriers entry, robustness, unclear best practices for experimental design analysis, lack standardization. In this Review, we present systematic catalog different families spatial technologies; highlight their principles, power, limitations; give perspective suggestions on biggest challenges lay ahead incredibly powerful-but hard navigate-landscape.

Language: Английский

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Spatial profiling technologies illuminate the tumor microenvironment

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 404 - 420

Published: Feb. 16, 2023

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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Spatial biology of cancer evolution

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 295 - 313

Published: Dec. 9, 2022

Language: Английский

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Slide-tags enables single-nucleus barcoding for multimodal spatial genomics

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 101 - 109

Published: Dec. 13, 2023

Abstract Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding how complex tissues are constructed 1–6 . However, missing from these measurements is ability to routinely easily spatially localize profiled cells. We developed a strategy, Slide-tags, in which single nuclei an intact tissue section tagged with spatial barcode oligonucleotides derived DNA-barcoded beads known positions. These can then be used as input into wide variety single-nucleus profiling assays. Application Slide-tags mouse hippocampus positioned at less than 10 μm resolution delivered whole-transcriptome data that indistinguishable quality ordinary RNA-sequencing data. To demonstrate applied human tissues, we performed assay on brain, tonsil melanoma. revealed cell-type-specific varying across cortical layers contextualized receptor–ligand interactions driving B cell maturation lymphoid tissue. A major benefit it adaptable almost any single-cell measurement technology. As proof principle, multiomic open chromatin, RNA T receptor (TCR) sequences same cells metastatic melanoma, identifying transcription factor motifs cancer state transitions distinct microenvironments. offers universal platform for importing compendium established genomics repertoire.

Language: Английский

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Spatial single-cell mass spectrometry defines zonation of the hepatocyte proteome

Nature Methods, Journal Year: 2023, Volume and Issue: 20(10), P. 1530 - 1536

Published: Oct. 1, 2023

Single-cell proteomics by mass spectrometry is emerging as a powerful and unbiased method for the characterization of biological heterogeneity. So far, it has been limited to cultured cells, whereas an expansion complex tissues would greatly enhance insights. Here we describe single-cell Deep Visual Proteomics (scDVP), technology that integrates high-content imaging, laser microdissection multiplexed spectrometry. scDVP resolves context-dependent, spatial proteome murine hepatocytes at current depth 1,700 proteins from cell slice. Half was differentially regulated in manner, with protein levels changing dramatically proximity central vein. We applied machine learning classes images, which subsequently inferred imaging data alone. applicable healthy diseased complements other omics technologies.

Language: Английский

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Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 30, 2023

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis poorly understood. The heritability estimate of MDD 30-40%, suggesting genetics alone do not account for most the risk major depression. Another factor known to associate with involves environmental stressors such as childhood adversity recent life stress. Recent studies have emerged show biological impact factors in other stress-related disorders mediated by variety epigenetic modifications. These modification alterations contribute abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission neuroglia dysfunction, which are involved pathophysiology MDD. Furthermore, marks been associated diagnosis treatment evaluation modifications holds promise further understanding heterogeneous etiology complex phenotypes MDD, may identify new therapeutic targets. Here, we review preclinical clinical findings, including DNA methylation, histone modification, noncoding RNA, RNA chromatin remodeling In addition, elaborate on contribution these mechanisms pathological trait variability depression discuss how can be exploited purposes.

Language: Английский

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