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@ARTICLE{Xu:280257,
      author       = {Xu, Jishu and Hörner, Michaela and Atienza, Elena Buena
                      and Manibarathi, Kalaivani and Nagel, Maike and Hauser,
                      Stefan and Admard, Jakob and Casadei, Nicolas and Ossowski,
                      Stephan and Schuele, Rebecca},
      title        = {{L}ong-read {RNA}-sequencing reveals transcript-specific
                      regulation in human-derived cortical neurons.},
      journal      = {Open biology},
      volume       = {15},
      number       = {7},
      issn         = {2046-2441},
      address      = {London},
      publisher    = {Royal Society Publishing},
      reportid     = {DZNE-2025-00935},
      pages        = {250200},
      year         = {2025},
      abstract     = {Long-read RNA sequencing has transformed transcriptome
                      analysis by enabling comprehensive mapping of full-length
                      transcripts, providing an unprecedented resolution of
                      transcript diversity, alternative splicing and
                      transcript-specific regulation. In this study, we employed
                      nanopore long-read RNA sequencing to profile the
                      transcriptomes of three cell types commonly used to model
                      brain disorders, human fibroblasts, induced pluripotent stem
                      cells and stem cell-derived cortical neurons, identifying
                      extensive transcript diversity with 15 072 transcripts in
                      stem cell-derived cortical neurons, 13 048 in fibroblasts
                      and 12 759 in induced pluripotent stem cells. Our analyses
                      uncovered 35 519 differential transcript expression events
                      and 5135 differential transcript usage events, underscoring
                      the complexity of transcriptomic regulation across these
                      cell types. Importantly, by integrating differential
                      transcript expression and usage analyses, we gained deeper
                      insights into transcript dynamics that are not captured by
                      gene-level expression analysis alone. Differential
                      transcript usage analysis highlighted transcript-specific
                      changes in disease-relevant genes such as APP, KIF2A and
                      BSCL2, associated with Alzheimer's disease, neuronal
                      migration disorders and degenerative axonopathies,
                      respectively. This added resolution emphasizes the
                      significance of transcript-level variations that often
                      remain hidden in traditional differential gene expression
                      analyses. Overall, our work provides a framework for
                      understanding transcript diversity in both pluripotent and
                      specialized cell types, which can be used to investigate
                      transcriptomic changes in disease states in future work.
                      Additionally, this study underscores the utility of
                      differential transcript usage analysis in advancing our
                      understanding of neurodevelopmental and neurodegenerative
                      diseases, paving the way for identifying transcript-specific
                      therapeutic targets.},
      keywords     = {Humans / Neurons: metabolism / Neurons: cytology / Sequence
                      Analysis, RNA: methods / Transcriptome / Induced Pluripotent
                      Stem Cells: metabolism / Induced Pluripotent Stem Cells:
                      cytology / Gene Expression Profiling: methods / Gene
                      Expression Regulation / Fibroblasts: metabolism /
                      Fibroblasts: cytology / Cerebral Cortex: cytology / Cerebral
                      Cortex: metabolism / Alternative Splicing / alternative
                      splicing (Other) / human-derived cortical neurons (Other) /
                      induced pluripotent stem cells (Other) / long-read
                      RNA-sequencing (Other) / transcript usage (Other) /
                      transcriptomics (Other)},
      cin          = {AG Hauser},
      ddc          = {570},
      cid          = {I:(DE-2719)1210016},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40735840},
      pmc          = {pmc:PMC12308531},
      doi          = {10.1098/rsob.250200},
      url          = {https://pub.dzne.de/record/280257},
}