RT Journal Article
SR Electronic
T1 The spatial landscape of gene expression isoforms in tissue sections
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.24.252296
DO 10.1101/2020.08.24.252296
A1 Kevin Lebrigand
A1 Joseph Bergenstråhle
A1 Kim Thrane
A1 Annelie Mollbrink
A1 Konstantinos Meletis
A1 Pascal Barbry
A1 Rainer Waldmann
A1 Joakim Lundeberg
YR 2022
UL http://biorxiv.org/content/early/2022/01/05/2020.08.24.252296.abstract
AB In situ capturing technologies add tissue context to gene expression data, with the potential of providing a greater understanding of complex biological systems. However, splicing variants and fulllength sequence heterogeneity cannot be characterized at spatial resolution with current transcriptome profiling methods. To that end, we introduce Spatial Isoform Transcriptomics (SiT), an explorative method for characterizing spatial isoform variation and sequence heterogeneity. We show in mouse brain how SIT can be used to profile isoform expression and sequence heterogeneity in different areas of the tissue. SiT reveals regional isoform switching of Plp1 gene between different layers of the olfactory bulb, and use of external single cell data allowed to nominate cell types expressing each isoform. Furthermore, SiT identifies differential isoform usage for several major genes implicated in brain function (Snap25, Bin1, Gnas) that we independently validated by in situ sequencing. SiT also provides for the first time an in-depth A-to-I RNA editing map of the adult mouse brain. Data exploration can be performed through an online resource (https://www.isomics.eu), where isoform expression and RNA editing can be visualized in a spatial context.Competing Interest StatementJ.L., J.B. and K.T. are advisors to 10x Genomics Inc, which holds IP rights to the ST technology. J.B. is a shareholder of Cartana AB.