Chromatin accessibility profiling in tissue sections by spatial ATAC

Llorens-Bobadilla, E.; Zamboni, M.; Marklund, M.; Bhalla, N.; Chen, X.; Hartman, J.; Frisen, J.; Stahl, P. L.

doi:10.1101/2022.07.27.500203

Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.07.27.500203

Chromatin accessibility profiling in tissue sections by spatial ATAC

Llorens-Bobadilla, E.·Zamboni, M.·Marklund, M.·Bhalla, N.·Chen, X.·Hartman, J.·Frisen, J.·Stahl, P. L.

View original source ↗Export metadata ↓

Abstract

Current methods for epigenomic profiling are limited in the ability to obtain genome wide information with spatial resolution. Here we introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathological samples.

Source connections

Published article ↗

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Llorens-Bobadilla, E., Zamboni, M., Marklund, M., Bhalla, N., Chen, X., Hartman, J., Frisen, J., Stahl, P. L.. 2022-07-29. Chromatin accessibility profiling in tissue sections by spatial ATAC. https://doi.org/10.1101/2022.07.27.500203

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A Y-specific translocated gsdf copy is a candidate master sex-determining gene in common dab (Limanda limanda)

Sex-determining systems in flatfishes are highly diverse, and even closely related species can differ in both sex-determining loci and heterogametic systems. In common dab (Limanda limanda), the genetic basis of sex determination has not yet been established. Here, we investigated sex determination using pooled whole-genome sequencing combined with long-read genome sequencing of females and males from Iceland and Norway. Genome-wide allele-frequency analyses identified sex-associated regions consistent with male heterogamety (XX/XY), with the strongest signal on chromosome 16. Comparison of the existing reference assembly, which represents an X haplotype at this locus, with a haplotype-resolved male PacBio HiFi assembly revealed a [~]21.5 kb Y-specific insertion on chromosome 16. The insertion showed complete coverage in male pools but little or no coverage in female pools from either population. It contained a translocated genomic segment including a copy of gonadal soma-derived factor (gsdf) and a predicted gene of unknown function. Comparative genomic analyses were consistent with this segment originating from an autosomal gsdf-containing region on chromosome 1. Given the recurrent recruitment of gsdf as a sex-determining factor in teleosts, we designate the Y-linked copy gsdfY and identify it as the strongest candidate for the master sex-determining gene in common dab. Additional broad sex-associated differentiation on chromosome 19 was restricted to the Icelandic samples and may reflect population-specific expansion of the sex-linked region, although its structural basis remains unresolved. Together, these findings provide the first genomic characterization of sex determination in common dab and demonstrate how gene duplication and translocation can contribute to the evolution of novel sex-determining systems in flatfishes.

genomics↗

bioRxiv2026

A population-scale isoform atlas enables isoform-based trait association and regulatory analysis in lettuce

Genomic variation shapes phenotypic diversity, yet how genetic variation contributes to transcript isoform diversity remains poorly understood at the population scale. Here, we integrated transcriptomic data from 240 lettuce accessions with a lettuce pangenome to construct a comprehensive pan isoform atlas comprising 531,657 isoforms from 49,729 transcribed loci. Isoform presence absence variation (iPAV) captured extensive transcript diversification during domestication and horticultural differentiation, providing additional resolution beyond locus-level analyses, particularly within loci shared across the population. To facilitate the systematic analysis of isoform trait associations, we developed ISONET-GWAS, a computational framework that integrates isoform-based association mapping, functional annotation, and network-based candidate prioritization. ISONET-GWAS recovered the known chlorophyll regulator LsGLK, identified 455 metabolite isoform associations across 77 metabolites, and prioritized candidate regulators of chlorophyll metabolism supported by functional validation. Genome-wide splicing quantitative trait locus (sQTL) mapping identified 10,498 sQTL associations, revealing widespread distal genetic associations with alternative splicing and candidate trans-sQTL hotspots. Notably, we identified a trans-sQTL hotspot overlapping LsPPR, which encodes a pentatricopeptide repeat RNA-binding protein. Perturbation of LsPPR resulted in widespread changes in alternative splicing of floweing-related genes, accompanied by delayed bolting and flowering and altered splicing of flowering-related genes. Together, our study establishes a population-scale pan-isoform resource and a broadly applicable analytical strategy for isoform-level trait association, candidate prioritization, and complementary analysis of the genetic regulation of alternative splicing in crops.

genomics↗

bioRxiv2026

Lifestyle-mediated shifts in the gut microbiome and host genetics modulate gene expression in intestinal organoids

Industrialization-associated shifts in the gut microbiome have been linked to disease, but the mechanisms by which microbial communities influence host gene regulation remain poorly understood. We developed a live microbiome-colonic organoid (colonoid) co-culture system to investigate genotype-dependent host responses to gut microbial community variation. Colonoid 2D monolayers from healthy donors were co-cultured with live gut microbial communities from individuals living urban or rural lifestyles, followed by RNA-sequencing. Urban and rural microbiomes elicited largely shared transcriptional responses, however they induced distinct host genetic effects on gene expression. We identified 511 host genes with microbiome-dependent allele-specific expression (ASE) which were involved in epithelial architecture, cell-matrix interactions and structural integrity. Notably, 149 host genes had distinct allelic effects between Urban and Rural microbiomes (urban-rural condition specific ASE or cASE), revealing genotype-dependent host responses to lifestyle-associated microbiomes. Urban-rural cASE was associated with microbial community composition, predominantly involving Prevotella and Bacteroides species. Targeted Prevotella copri spike-in recapitulated Prevotella-associated allelic effects at specific loci, including one in the IBD-associated autophagy gene, ATG4B. Together, these findings establish an experimental framework to investigate genotype-by-microbiome interactions, and demonstrate that lifestyle-mediated shifts in the microbiome modify host cis-regulatory genetic effects on gene expression.

genomics↗