Universität zu Köln

Boileau, Etienne, Li, Xue, Naarmann-de Vries, Isabel S., Becker, Christian, Casper, Ramona, Altmueller, Janine, Leuschner, Florian and Dieterich, Christoph (2022). Full-Length Spatial Transcriptomics Reveals the Unexplored Isoform Diversity of the Myocardium Post-MI. Front. Genet., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-8021

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boileau, Etienne UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Xue UNSPECIFIED UNSPECIFIED UNSPECIFIED Naarmann-de Vries, Isabel S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Casper, Ramona UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Leuschner, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-688204
DOI:	10.3389/fgene.2022.912572
Journal or Publication Title:	Front. Genet.
Volume:	13
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-8021
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; HEART DEVELOPMENT; RNA; GENOME Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68820