Tissular chromatin states cartography based on double-barcoded DNA arrays capturing unloaded PA-Tn5 Transposase

Le 18 juin 2025 à 10h00 Séminaire

Background

Developments in spatially-resolved transcriptomics (SrT), and more recently on spatially-resolved epigenomics are providing means to interrogate organ/tissue architecture from the angle of the gene programs defining their molecular complexity. Despite the proved performance of the available spatially-resolved omics technologies in a variety of tissue samples; there are still major challenges to address. Indeed, beyond the over-discussed aspects related to the resolution of these technologies, their capacity to access to other type of molecular readouts (e.g. chromatin accessibility, epigenetics), their technical limitations issued from the way in which the biological specimens were preserved (FFPE vs fresh frozen tissues), but also their current elevated costs, make of these technologies applicable to few tissue sections, thus avoiding to generate multi-omic integrative views of their molecular complexity.

Results

Here, we present a strategy for capturing chromatin histone modification signatures across tissue sections by taking advantage of a double-barcoded DNA arrays design compatible with in situ protein A-Transposase Tn5 tagmentation. This approach has been validated in presence of fresh-frozen mouse brain tissues but also in decalcified formalin-fixed paraffin-embedded (FFPE) mouse paws samples, where either the histone modification H3K4 tri-methylation or H3K27-acethylation has been used as proxy for interrogating active promoter signatures. Furthermore, since combinatorial enrichment of multiple histone modifications were shown to code for various states of gene transcriptional status (active, bivalent, repressed), we have integrated several histone modifications issued from consecutive mouse embryos to reveal changes in chromatin states across the tissue

Conclusions
Overall, this spatial epigenomics technology combined with the use of a spatial chromatin states analytical strategy paves the way for future epigenetics studies for addressing tissue architecture complexity.