Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus DOI Creative Commons
Liangfu Chen, Hannah K. Long, Minhee Park

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(9), P. 1446 - 1461.e6

Published: March 29, 2023

Summary

Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate SOX9 expression at genomic distances over 1.25 Mb. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. observed pronounced changes between cell types. Subsequent analysis single-chromatin fiber traces revealed that these ensemble-average differences arise through the frequency commonly sampled topologies. further identified two CTCF-bound elements, internal topologically associating domain, which promote stripe formation, are positioned near domain's geometric center, and bridge enhancer-promoter contacts a series loops. Ablation elements results diminished altered domain-wide contacts. Polymer models with uniform loading across domain frequent cohesin collisions recapitulate this multi-loop, centrally clustered geometry. Together, we provide mechanistic insights into architectural formation gene regulation ultra-long ranges.

Language: Английский

Exploring tissue architecture using spatial transcriptomics DOI
Anjali Rao, Dalia Barkley, Gustavo S. França

et al.

Nature, Journal Year: 2021, Volume and Issue: 596(7871), P. 211 - 220

Published: Aug. 11, 2021

Language: Английский

Citations

1086

Methods and applications for single-cell and spatial multi-omics DOI Open Access
Katy Vandereyken, Alejandro Sifrim, Bernard Thienpont

et al.

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

Published: March 2, 2023

Language: Английский

Citations

626

An introduction to spatial transcriptomics for biomedical research DOI Creative Commons

Cameron G. Williams,

Hyun Jae Lee,

Takahiro Asatsuma

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: June 27, 2022

Abstract Single-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact viable from tissue. This precluded many cell types study largely destroys spatial context that could otherwise inform analyses of identity function. An increasing number platforms now facilitate spatially resolved, high-dimensional assessment gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes method, which either record locations hybridized mRNA molecules tissue, image positions themselves prior assessment, or employ arrays probes pre-determined location. We review sizes tissue area can assessed, their resolution, genes profiled. discuss if preservation influences choice platform, provide guidance on whether specific may better suited discovery screens hypothesis testing. Finally, bioinformatic methods analysing transcriptomic data, including pre-processing, integration with existing inference cell-cell interactions. Spatial -omics are already improving our understanding human tissues research, diagnostic, therapeutic settings. To build upon these recent advancements, entry-level those seeking own research.

Language: Английский

Citations

467

Spatial omics and multiplexed imaging to explore cancer biology DOI
Sabrina M. Lewis, Marie-Liesse Asselin-Labat, Quan Nguyen

et al.

Nature Methods, Journal Year: 2021, Volume and Issue: 18(9), P. 997 - 1012

Published: Aug. 2, 2021

Language: Английский

Citations

441

Understanding 3D genome organization by multidisciplinary methods DOI
Ivana Jerković, Giacomo Cavalli

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(8), P. 511 - 528

Published: May 5, 2021

Language: Английский

Citations

299

The emerging landscape of spatial profiling technologies DOI
Jeffrey R. Moffitt, Emma Lundberg, Holger Heyn

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 741 - 759

Published: July 20, 2022

Language: Английский

Citations

279

The expanding vistas of spatial transcriptomics DOI
Luyi Tian, Fei Chen, Evan Z. Macosko

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 41(6), P. 773 - 782

Published: Oct. 3, 2022

Language: Английский

Citations

273

The dawn of spatial omics DOI
Dario Bressan, Giorgia Battistoni, Gregory J. Hannon

et al.

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

Citations

260

Spatial transcriptomics of planktonic and sessile bacterial populations at single-cell resolution DOI
Daniel Dar,

Nina Dar,

Long Cai

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6556)

Published: Aug. 12, 2021

Capturing the heterogeneous phenotypes of microbial populations at relevant spatiotemporal scales is highly challenging. Here, we present par-seqFISH (parallel sequential fluorescence in situ hybridization), a transcriptome-imaging approach that records gene expression and spatial context within microscale assemblies single-cell molecule resolution. We applied this to opportunistic pathogen Pseudomonas aeruginosa, analyzing about 600,000 individuals across dozens conditions planktonic biofilm cultures. identified numerous metabolic- virulence-related transcriptional states emerged dynamically during growth, as well spatially resolved metabolic heterogeneity sessile populations. Our data reveal distinct physiological can coexist same just several micrometers away, underscoring importance microenvironment. results illustrate complex dynamics new way studying them high

Language: Английский

Citations

212

Spatial epigenome–transcriptome co-profiling of mammalian tissues DOI Creative Commons
Di Zhang, Yanxiang Deng, Petra Kukanja

et al.

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

Citations

211