The spatial landscape of gene expression isoforms in tissue sections.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
08 05 2023
08 05 2023
Historique:
accepted:
23
02
2023
revised:
06
02
2023
received:
25
07
2022
medline:
9
5
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
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 full-length 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 using long-read sequencing. 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 the use of external single-cell data allows the nomination of cell types expressing each isoform. Furthermore, SiT identifies differential isoform usage for several major genes implicated in brain function (Snap25, Bin1, Gnas) that are 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.
Identifiants
pubmed: 36928528
pii: 7079641
doi: 10.1093/nar/gkad169
pmc: PMC10164556
doi:
Substances chimiques
Protein Isoforms
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e47Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Nat Commun. 2019 Jul 12;10(1):3094
pubmed: 31300657
Science. 2016 Jul 1;353(6294):78-82
pubmed: 27365449
Genome Res. 2019 Sep;29(9):1453-1463
pubmed: 31427386
Cell. 2018 Aug 9;174(4):999-1014.e22
pubmed: 30096314
J Cell Mol Med. 2018 Jan;22(1):576-588
pubmed: 28990332
Genome Biol. 2022 Jan 18;23(1):27
pubmed: 35042561
Sci Rep. 2017 Oct 20;7(1):13654
pubmed: 29057893
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):9726-9731
pubmed: 30201725
BMC Genomics. 2020 Jul 14;21(1):482
pubmed: 32664861
Nat Biotechnol. 2020 Jun;38(6):708-714
pubmed: 32518404
Cell. 2022 May 12;185(10):1777-1792.e21
pubmed: 35512705
Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2318-2327
pubmed: 30659150
Cell. 2020 Dec 10;183(6):1665-1681.e18
pubmed: 33188776
Nucleic Acids Res. 2021 May 21;49(9):e50
pubmed: 33544846
Nucleic Acids Res. 2014 Jan;42(Database issue):D109-13
pubmed: 24163250
Science. 2019 Mar 29;363(6434):1463-1467
pubmed: 30923225
Nat Rev Mol Cell Biol. 2017 Jul;18(7):437-451
pubmed: 28488700
Nucleic Acids Res. 2013 Jan;41(Database issue):D996-D1008
pubmed: 23193282
Heliyon. 2023 Apr 17;9(5):e15306
pubmed: 37131430
Front Cell Neurosci. 2015 Mar 05;9:69
pubmed: 25798088
Bioessays. 2020 Oct;42(10):e1900221
pubmed: 32363691
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1510-4
pubmed: 7878010
Nat Rev Neurosci. 2013 Apr;14(4):233-47
pubmed: 23481482
Nat Biotechnol. 2018 Oct 15;:
pubmed: 30320766
Genome Biol. 2020 Feb 7;21(1):30
pubmed: 32033565
Cell Mol Life Sci. 2021 Jul;78(14):5605-5630
pubmed: 34100982
Nat Commun. 2021 Jan 19;12(1):463
pubmed: 33469025
Sci Adv. 2020 Jun 26;6(26):eabb3446
pubmed: 32637622
Genome Res. 2017 May;27(5):737-746
pubmed: 28100585
RNA Biol. 2021 Jul;18(7):999-1013
pubmed: 33393416
J Biol Chem. 2001 Nov 9;276(45):42162-71
pubmed: 11533047
Curr Osteoporos Rep. 2015 Jun;13(3):146-58
pubmed: 25851935
Commun Biol. 2023 May 24;6(1):558
pubmed: 37225862
Curr Genomics. 2007 Sep;8(6):398-414
pubmed: 19412439
Nat Biotechnol. 2021 Mar;39(3):313-319
pubmed: 33288904
BMC Biol. 2020 Jan 14;18(1):6
pubmed: 31937309
Cell Rep. 2018 Dec 4;25(10):2689-2703.e3
pubmed: 30517858
Nature. 2010 Nov 11;468(7321):244-52
pubmed: 21068833
Traffic. 2002 Jul;3(7):452-60
pubmed: 12047553
Nat Commun. 2020 Aug 12;11(1):4025
pubmed: 32788667
Front Genet. 2022 Jul 22;13:912572
pubmed: 35937994
Biochim Biophys Acta. 2009 Jun;1792(6):548-54
pubmed: 19376225
Trends Genet. 2016 Mar;32(3):165-175
pubmed: 26803450
Front Mol Biosci. 2018 Feb 12;5:12
pubmed: 29484299
Hum Mol Genet. 2009 Jan 1;18(1):118-27
pubmed: 18836209
J Biol Chem. 2020 Dec 25;295(52):18199-18212
pubmed: 33100268
Trends Cell Biol. 2009 Jul;19(7):347-55
pubmed: 19524440
Methods Mol Biol. 2021;2181:309-330
pubmed: 32729088
Bioinformatics. 2018 Sep 15;34(18):3094-3100
pubmed: 29750242
J Hum Genet. 2020 Jan;65(1):3-10
pubmed: 31474751
Curr Opin Neurobiol. 2019 Aug;57:26-31
pubmed: 30703685
Mol Psychiatry. 2013 Nov;18(11):1225-34
pubmed: 23399914
Mol Neurodegener. 2016 Aug 03;11(1):59
pubmed: 27488240
Sci Rep. 2019 Apr 25;9(1):6403
pubmed: 31024034