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Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue
Open accessAbstract
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.
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“Emerging long-read sequencing approaches enable us to profile cellular transcriptomes at isoform resolution,8,31,32,33 thus providing new opportunities to model the relationships between isoforms using co-expression network analysis.”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [33]
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Cites
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181
La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0414-6 · Cited by 4,118
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 3,971
Real-Time DNA Sequencing from Single Polymerase Molecules
Eid, J., Fehr, A., Gray, J., Luong, K., Lyle, J., Otto, G., Peluso, P., Rank, D., Baybayan, P., Bettman, B., et al. (2009) · Science · doi:10.1126/science.1162986 · Cited by 3,732
Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells
Klein, A. M., Mazutis, L., Akartuna, I., Tallapragada, N., Veres, A., Li, V., Peshkin, L., Weitz, D. A., & Kirschner, M. W. (2015) · Cell · doi:10.1016/j.cell.2015.04.044 · Cited by 3,356
Research works printed but not linked: 1
- Herrmann, C. J. et al. PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3′ end sequencing. Nucleic Acids Res. 48, D174–D179 (2019).
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Sasagawa, Y., Iwayama, Y., Yano, M., & Nikaido, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.19.670999
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Dam, S. H., Olsen, L. R., & Vitting-Seerup, K. (2023) · Figshare · doi:10.6084/m9.figshare.24406762
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Liu, Y., Feng, W., Aikedan, A., Lee, S.-I., Bhagwat, M., Nagiri, R. K., Wong, M. Y., Amin, S., Qu, W., Zhu, J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.24.707791
Self-citationMichielsen, L., Hsu, J., Joglekar, A., Belchikov, N., Reinders, M. J. T., Tilgner, H., & Mahfouz, A. E. (2026) · Genome biology · doi:10.1186/s13059-026-04015-z · Cited by 3
Self-citationZehra, B., Bineshaq, S., Faizan, M., Eldesouky, M., Vinod, N., Mohamed, N., Vijayakumar, A., Aleksandrova, I., Tambi, R., Sabeel, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.31.715736
Multiscale analysis of transcriptome : methodological and algorithmic developments
Liehrmann, A. (2023) · theses.fr (ABES) · doi:10.70675/bcfe650ez1176z4db0zb5aczb48c0eae17b0
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Qu, W., Li, F., Jang, M. W., Ye, P., Cordes, E., Aikedan, A., Hu, W., Nagiri, R. K., Wong, M. Y., Luo, W., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.02.736124
Self-citationCoordinated pre-mRNA processing at the single-transcript level
Sen, L. P., & Neugebauer, K. M. (2026) · Trends in Genetics · doi:10.1016/j.tig.2026.06.005
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Essa, I. M., Saranraj, P., Lokeshwari, B., Cardoso, A. M., Kesavardhini, K., & Sivasakthivelan, P. (2026) · Interdisciplinary biotechnological advances · doi:10.1007/978-981-95-9011-7_9
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Pan, T., Lu, L., & Gao, R. (2026) · Journal of Clinical Investigation · doi:10.1172/jci207476
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Kadam, U. S., Zhou, Z., Irudayaraj, J., Cho, I., & Hong, J. C. (2026) · ACS Omega · doi:10.1021/acsomega.6c07239
Kim, S., & Lee, J. (2024) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.10939706
Metadata
- Authors
- Hardwick, S. A., Hu, W., Joglekar, A., Fan, L., Collier, P. G., Foord, C., Balacco, J., Lanjewar, S., Sampson, M. M., Koopmans, F., Prjibelski, A. D., Mikheenko, A., Belchikov, N., Jarroux, J., Lucas, A. B., Palkovits, M., Luo, W., Milner, T. A., Ndhlovu, L. C., Smit, A. B., Trojanowski, J. Q., Lee, V. M. Y., Fedrigo, O., Sloan, S. A., Tombácz, D., Ross, M. E., Jarvis, E., Boldogkői, Z., Gan, L., & Tilgner, H. U.
- Affiliations
- Weill Cornell Medicine (US)
- Rockefeller University (US)
- Emory University (US)
- Amsterdam Neuroscience (NL)
- St Petersburg University (RU)
- Agilent Technologies (United States) (US)
- Semmelweis University (HU)
- University of Pennsylvania (US)
- University of Szeged (HU)
- Corresponding author
- Tilgner, Hagen U.
- ORCID
- Hardwick, Simon A.
- Hu, Wen
- Joglekar, Anoushka
- Fan, Li
- Foord, Careen
- Balacco, Jennifer
- Lanjewar, Samantha
- Sampson, Maureen McGuirk
- Koopmans, Frank
- Prjibelski, Andrey D.
- Mikheenko, Alla
- Belchikov, Natan
- Jarroux, Julien
- Palkovits, Miklós
- Luo, Wenjie
- Milner, Teresa A.
- Ndhlovu, Lishomwa C.
- Smit, August B.
- Trojanowski, John Q.
- Lee, Virginia M. Y.
- Fedrigo, Olivier
- Sloan, Steven A.
- Tombácz, Dóra
- Ross, M. Elizabeth
- Jarvis, Erich
- Boldogkői, Zsolt
- Gan, Li
- Tilgner, Hagen U.
- Venue
- Nature Biotechnology
- Published
- 2022-03-07
- Volume
- 40
- Issue
- 7
- Pages
- 1082-1092
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC9287170
- OpenAlex
- W4220958064
- Cited by
- 119
- References
- 59
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 32 · 2023: 26 · 2022: 11
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Department of Health | National Health and Medical Research Council (APP1156531)
- Saint Petersburg State University (PURE 73023672)
- Semmelweis Egyetem (2017-1.2.1-NKP-2017-00002)
- Hungarian Brain Research Program, The Human Brain Tissue Bank, Semmelweis University
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (DA08259, U01 DA53625, U01 DA053625-01)
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (HL136520)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (UM1AI164599)
- U.S. Department of Health & Human Services | National Institutes of Health (U19 AG062418, R01AG051390, U54NS100717, R01AG054214)
- Howard Hughes Medical Institute
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH125956, 1RF1MH121267-01)
- Brain and Behavior Research Foundation (28172)
- Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal (FK128252, K128247)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (1R01NS105477, U54NS11717)
- U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD067244)
- Feil Family Foundation
- JPB Foundation
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (1R01GM135247-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- alternative splicing, barcoding, frozen brain tissue, human frontal cortex, autism spectrum disorder, long-read sequencing, microfluidics, target enrichment
- MeSH terms
- Brain, Exons, Humans, RNA, Alternative Splicing, Sequence Analysis, RNA, Protein Isoforms
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