Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies DOI Creative Commons
Yubin Yan,

Yuhan Tian,

Zefeng Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 13, 2023

Abstract Retrocopies are gene duplicates arising from reverse transcription of mature mRNA transcripts and their insertion back into the genome. While long being regarded as processed pseudogenes, more functional retrocopies have been discovered. How stripped- down recover expression capability become paralogs continually intrigues evolutionary biologists. Here, we investigated function evolution in context three-dimensional (3D) genome organization. By mapping retrocopy-parent pairs onto sequencing-based imaging-based chromatin contact maps human mouse cell lines Hi-C interaction five other mammals, found that parental genes show a higher-than-expected interchromosomal colocalization frequency. The spatial interactions between occur frequently at loci active subcompartments near nuclear speckles. Accordingly, colocalized actively transcribed translated, evolutionarily conserved than noncolocalized ones. may result permissive epigenetic environment shared regulatory elements with genes. Population genetic analysis retroposed copy number variants (retroCNVs) populations revealed retrocopy insertions not entirely random regard to retroCNVs likely reach high frequencies, suggesting both bias natural selection contribute pairs. Further dissection implies reduced efficacy, rather positive selection, contributes elevated allele frequency retroCNVs. Overall, our results hint role “resurrection” initially neutral retrocopies.

Language: Английский

Lifelong restructuring of 3D genome architecture in cerebellar granule cells DOI
Longzhi Tan, Jenny Shi, Siavash Moghadami

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6662), P. 1112 - 1119

Published: Sept. 7, 2023

The cerebellum contains most of the neurons in human brain and exhibits distinctive modes development aging. In this work, by developing our single-cell three-dimensional (3D) genome assay—diploid chromosome conformation capture, or Dip-C—into population-scale (Pop-C) virus-enriched (vDip-C) modes, we resolved first 3D structures single cerebellar cells, created life-spanning atlases for both humans mice, jointly measured transcriptome chromatin accessibility during development. We found that although granule mature early postnatal life, architecture gradually remodels throughout establishing ultra–long-range intrachromosomal contacts specific interchromosomal are rarely seen neurons. These results reveal unexpected evolutionarily conserved molecular processes underlie features neural aging across mammalian life span.

Language: Английский

Citations

42
Computational methods for analysing multiscale 3D genome organization DOI
Yang Zhang, Lorenzo Boninsegna, Muyu Yang

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 123 - 141

Published: Sept. 6, 2023

Language: Английский

Citations

37
Biophysical modeling with variational autoencoders for bimodal, single-cell RNA sequencing data DOI Creative Commons
Maria Carilli, Gennady Gorin,

Yongin Choi

et al.

Nature Methods, Journal Year: 2024, Volume and Issue: 21(8), P. 1466 - 1469

Published: July 25, 2024

Language: Английский

Citations

16
Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits DOI Creative Commons
Loïc Binan, Aiping Jiang,

Serwah Danquah

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Highlights•Perturb-FISH combines spatial transcriptomics and readout of CRISPR perturbation•We recover the effects genetic perturbation on transcriptome single cells•We find specific networks related to cell neighbors in tissue•We connect time-resolved imaging phenotypes after perturbationSummaryPooled optical screens have enabled study cellular interactions, morphology, or dynamics at massive scale, but they not yet leveraged power highly plexed single-cell resolved transcriptomic readouts inform molecular pathways. Here, we present a combination with parallel detection situ amplified guide RNAs (Perturb-FISH). Perturb-FISH recovers intracellular that are consistent RNA-sequencing-based (Perturb-seq) screen lipopolysaccharide response cultured monocytes, it uncovers intercellular density-dependent regulation innate immune response. Similarly, three-dimensional xenograft models, identifies tumor-immune interactions altered by knockout. When paired functional separate autism spectrum disorder risk genes human-induced pluripotent stem (hIPSC) astrocytes, shows common calcium activity their associated dysregulated is thus general method for studying associations biology resolution.Graphical abstract

Language: Английский

Citations

1
Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits DOI Creative Commons
Loïc Binan,

Serwah Danquah,

Vera Valakh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Pooled optical screens have enabled the study of cellular interactions, morphology, or dynamics at massive scale, but not yet leveraged power highly-plexed single-cell resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging spatial transcriptomics with parallel detection in situ amplified guide RNAs. We show that Perturb-FISH recovers intracellular effects are consistent Perturb-seq results a screen lipopolysaccharide response cultured monocytes, and uncover new intercellular density-dependent regulation innate immune response. further pair functional readout autism spectrum disorder risk genes, showing common calcium activity phenotypes induced pluripotent stem cell derived astrocytes their associated genetic interactions dysregulated is thus generally applicable method for studying associations biology resolution.

Language: Английский

Citations

19
Enablers and challenges of spatial omics, a melting pot of technologies DOI Creative Commons
Theodore Alexandrov, Julio Sáez-Rodríguez, Sinem K. Saka

et al.

Molecular Systems Biology, Journal Year: 2023, Volume and Issue: 19(11)

Published: Oct. 16, 2023

Abstract Spatial omics has emerged as a rapidly growing and fruitful field with hundreds of publications presenting novel methods for obtaining spatially resolved information any data type on spatial scales ranging from subcellular to organismal. From technology development perspective, is highly interdisciplinary that integrates imaging omics, molecular analyses, sequencing mass spectrometry, image analysis bioinformatics. The emergence this not only opened window into biology, but also created multiple opportunities, questions, challenges method developers. Here, we provide the perspective developers what makes unique. After providing brief overview state art, discuss technological enablers present our vision about future applications impact melting pot.

Language: Английский

Citations

18
Histone 4 lysine 20 tri-methylation: a key epigenetic regulator in chromatin structure and disease DOI Creative Commons

Alejandra Agredo,

Andrea L. Kasinski

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 21, 2023

Chromatin is a vital and dynamic structure that carefully regulated to maintain proper cell homeostasis. A great deal of this regulation dependent on histone proteins which have the ability be dynamically modified their tails via various post-translational modifications (PTMs). While multiple PTMs are studied often work in concert facilitate gene expression, here we focus tri-methylation H4 lysine 20 (H4K20me3) its function chromatin structure, cycle, DNA repair, development. The recent studies evaluated review shed light how H4K20me3 established by interacting partners interact with PTM involved diseases. Through analyzing current literature regulation, aim summarize knowledge highlights gaps remain field.

Language: Английский

Citations

13
Advances in the multimodal analysis of the 3D chromatin structure and gene regulation DOI Creative Commons

Man-Hyuk Han,

Jihyun Park, Minhee Park

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(4), P. 763 - 771

Published: April 25, 2024

Abstract Recent studies have demonstrated that the three-dimensional conformation of chromatin plays a crucial role in gene regulation, with aberrations potentially leading to various diseases. Advanced methodologies revealed link between and biological function. This review divides these into sequencing-based imaging-based methodologies, tracing their development over time. We particularly highlight innovative techniques facilitate simultaneous mapping RNAs, histone modifications, proteins within context 3D architecture chromatin. multimodal integration substantially improves our ability establish robust connection spatial arrangement molecular components nucleus functional roles. Achieving comprehensive understanding regulation requires capturing diverse data modalities individual cells, enabling direct inference relationships components. In this context, technologies emerged as an especially promising approach for gathering information across multiple same cell.

Language: Английский

Citations

4
Nuclear speckle biology: At the cross-roads of discovery and functional analysis DOI Creative Commons
Pankaj Chaturvedi, Andrew S. Belmont

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 91, P. 102438 - 102438

Published: Sept. 27, 2024

Language: Английский

Citations

4
Charting the tumor microenvironment with spatial profiling technologies DOI Open Access

Mattia Toninelli,

Grazisa Rossetti, Massimiliano Pagani

et al.

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(12), P. 1085 - 1096

Published: Sept. 4, 2023

Language: Английский

Citations

10