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Cited by 58Single-cell and spatial transcriptomicsRNA Research and SplicingGenomics and Phylogenetic Studies

Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq

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Rebboah, Elisabeth, Reese, Fairlie, Williams, Katherine, Balderrama-Gutierrez, Gabriela, McGill, Cassandra, Trout, Diane, Rodriguez, Isaryhia, Liang, Heidi +2 more·2021·Genome Biology
DOI 10.1186/s13059-021-02505-wPMC PMC8495978

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Abstract

The rise in throughput and quality of long-read sequencing should allow unambiguous identification of full-length transcript isoforms. However, its application to single-cell RNA-seq has been limited by throughput and expense. Here we develop and characterize long-read Split-seq (LR-Split-seq), which uses combinatorial barcoding to sequence single cells with long reads. Applied to the C2C12 myogenic system, LR-split-seq associates isoforms to cell types with relative economy and design flexibility. We find widespread evidence of changing isoform expression during differentiation including alternative transcription start sites (TSS) and/or alternative internal exon usage. LR-Split-seq provides an affordable method for identifying cluster-specific isoforms in single cells.

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  • Emerging long-read sequencing approaches enable profiling cellular transcriptomes at isoform resolution.

    “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 [31]

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Authors
Rebboah, E., Reese, F., Williams, K., Balderrama-Gutierrez, G., McGill, C., Trout, D., Rodriguez, I., Liang, H., Wold, B. J., & Mortazavi, A.
Affiliations
  • University of California, Irvine (US)
  • California Institute of Technology (US)
Corresponding author
Mortazavi, Ali
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2021-10-07
Volume
22
Issue
1
Pages
286-286
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-021-02505-w
PMC
PMC8495978
OpenAlex
W3202223582
Cited by
58
References
8
Citations by year
2026: 12 · 2025: 10 · 2024: 17 · 2023: 11 · 2022: 7 · 2021: 1
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Human Genome Research Institute (UM1HG009443)
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
combinatorial barcoding, alternative transcription start sites, alternative exon usage, C2C12 myoblasts, cell differentiation, single-cell genomics
MeSH terms
RNA-Seq, Animals, Cell Differentiation, Cell Line, Cell Nucleus, Chromatin, Models, Genetic, Transcription, Genetic, Myogenin, Genomics, Transcription Initiation Site, Mice, PAX7 Transcription Factor, Single-Cell Analysis, RNA Isoforms

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