Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue.

Alternative Splicing / genetics Brain / metabolism Exons / genetics Humans Protein Isoforms / genetics RNA / genetics Sequence Analysis, RNA

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
07 2022
Historique:
received: 29 06 2021
accepted: 20 01 2022
pubmed: 9 3 2022
medline: 20 7 2022
entrez: 8 3 2022
Statut: ppublish

Résumé

Single-nuclei RNA sequencing characterizes cell types at the gene level. However, compared to single-cell approaches, many single-nuclei cDNAs are purely intronic, lack barcodes and hinder the study of isoforms. Here we present single-nuclei isoform RNA sequencing (SnISOr-Seq). Using microfluidics, PCR-based artifact removal, target enrichment and long-read sequencing, SnISOr-Seq increased barcoded, exon-spanning long reads 7.5-fold compared to naive long-read single-nuclei sequencing. We applied SnISOr-Seq to adult human frontal cortex and found that exons associated with autism exhibit coordinated and highly cell-type-specific inclusion. We found two distinct combination patterns: those distinguishing neural cell types, enriched in TSS-exon, exon-polyadenylation-site and non-adjacent exon pairs, and those with multiple configurations within one cell type, enriched in adjacent exon pairs. Finally, we observed that human-specific exons are almost as tightly coordinated as conserved exons, implying that coordination can be rapidly established during evolution. SnISOr-Seq enables cell-type-specific long-read isoform analysis in human brain and in any frozen or hard-to-dissociate sample.

Identifiants

DOI: 10.1038/s41587-022-01231-3 PMID: 35256815 PMC: PMC9287170
pubmed: 35256815
doi: 10.1038/s41587-022-01231-3
pii: 10.1038/s41587-022-01231-3
pmc: PMC9287170
mid: NIHMS1800685
doi:

Substances chimiques

Protein Isoforms 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1082-1092

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL136520
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM135247
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI164559
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS100717
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA053625
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105477
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA008259
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA039080
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH121267
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125956
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG072758
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG051390
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS117170
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NICHD NIH HHS
ID : P01 HD067244
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS123562
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054214
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Simon A Hardwick (SA)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.

Wen Hu (W)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-0604-2119

Anoushka Joglekar (A)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-7818-6867

Li Fan (L)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.

Paul G Collier (PG)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.

Careen Foord (C)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.

Jennifer Balacco (J)

The Rockefeller University, New York, NY, USA.

Samantha Lanjewar (S)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
ORCID: 0000-0002-9227-3668

Maureen McGuirk Sampson (MM)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
ORCID: 0000-0003-1536-3229

Frank Koopmans (F)

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
ORCID: 0000-0002-4973-5732

Andrey D Prjibelski (AD)

Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.

Alla Mikheenko (A)

Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.

Natan Belchikov (N)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
Physiology, Biophysics & Systems Biology Program, Weill Cornell Medicine, New York, NY, USA.

Julien Jarroux (J)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.

Anne Bergstrom Lucas (AB)

Agilent Technologies, Santa Clara, CA, USA.

Miklós Palkovits (M)

Human Brain Tissue Bank, Semmelweis University, Budapest, Hungary.
ORCID: 0000-0003-0578-0387

Wenjie Luo (W)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0003-3752-8266

Teresa A Milner (TA)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

Lishomwa C Ndhlovu (LC)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.

August B Smit (AB)

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.

John Q Trojanowski (JQ)

Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
ORCID: 0000-0002-9239-8794

Virginia M Y Lee (VMY)

Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Olivier Fedrigo (O)

The Rockefeller University, New York, NY, USA.
ORCID: 0000-0002-6450-7551

Steven A Sloan (SA)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.

Dóra Tombácz (D)

Department of Medical Biology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
ORCID: 0000-0001-5520-2978

M Elizabeth Ross (ME)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0001-6440-8089

Erich Jarvis (E)

The Rockefeller University, New York, NY, USA.
ORCID: 0000-0001-8931-5049

Zsolt Boldogkői (Z)

Department of Medical Biology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

Li Gan (L)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.

Hagen U Tilgner (HU)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.
Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.
ORCID: 0000-0002-7058-3606

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Épissage alternatif › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Exons › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Isoformes de protéines › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Single-nuclei isoform RNA sequencing unlocks...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Single-nuclei isoform RNA sequencing unlocks...