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Full-length spatial transcriptomics reveals the unexplored isoform diversity of the myocardium post-MI

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Item Type:Article
Title:Full-length spatial transcriptomics reveals the unexplored isoform diversity of the myocardium post-MI
Creators Name:Boileau, E. and Li, X. and Naarmann-de Vries, I.S. and Becker, C. and Casper, R. and Altmüller, J. and Leuschner, F. and Dieterich, C.
Abstract:We introduce Single-cell Nanopore Spatial Transcriptomics (scNaST), a software suite to facilitate the analysis of spatial gene expression from second- and third-generation sequencing, allowing to generate a full-length near-single-cell transcriptional landscape of the tissue microenvironment. Taking advantage of the Visium Spatial platform, we adapted a strategy recently developed to assign barcodes to long-read single-cell sequencing data for spatial capture technology. Here, we demonstrate our workflow using four short axis sections of the mouse heart following myocardial infarction. We constructed a de novo transcriptome using long-read data, and successfully assigned 19,794 transcript isoforms in total, including clinically-relevant, but yet uncharacterized modes of transcription, such as intron retention or antisense overlapping transcription. We showed a higher transcriptome complexity in the healthy regions, and identified intron retention as a mode of transcription associated with the infarct area. Our data revealed a clear regional isoform switching among differentially used transcripts for genes involved in cardiac muscle contraction and tissue morphogenesis. Molecular signatures involved in cardiac remodeling integrated with morphological context may support the development of new therapeutics towards the treatment of heart failure and the reduction of cardiac complications.
Keywords:Spatial Transcriptomics, Single-Cell RNA Sequencing, Oxford Nanopore Technology, Myocardial Infarction, Visium Spatial, Animals, Mice
Source:Frontiers in Genetics
Publisher:Frontiers Media SA
Page Range:912572
Date:22 July 2022
Official Publication:https://doi.org/10.3389/fgene.2022.912572
PubMed:View item in PubMed

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