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@ARTICLE{Xu:279124,
      author       = {Xu, Jishu and Hörner, Michaela and Nagel, Maike and
                      Perhat, Perwin and Korneck, Milena and Noß, Marvin and
                      Hauser, Stefan and Schöls, Ludger and Admard, Jakob and
                      Nicolas, Casadei and Schüle-Freyer, Rebecca},
      title        = {{U}nravelling axonal transcriptional landscapes: insights
                      from induced pluripotent stem cell-derived cortical neurons
                      and implications for motor neuron degeneration},
      journal      = {Open biology},
      volume       = {15},
      number       = {6},
      issn         = {2046-2441},
      address      = {London},
      publisher    = {Royal Society Publishing},
      reportid     = {DZNE-2025-00684},
      pages        = {250101},
      year         = {2025},
      abstract     = {Neuronal function and pathology are deeply influenced by
                      the distinct molecular profiles of the axon and soma.
                      Traditional studies have often overlooked these differences
                      due to the technical challenges of compartment-specific
                      analysis. In this study, we employ a robust RNA-sequencing
                      approach, using microfluidic devices, to generate
                      high-quality axonal transcriptomes from induced pluripotent
                      stem cells-derived cortical neurons (CNs). We achieve high
                      specificity of axonal fractions, ensuring sample purity
                      without contamination. Comparative analysis revealed a
                      unique and specific transcriptional landscape in axonal
                      compartments, characterized by diverse transcript types,
                      including protein-coding mRNAs, RNAs encoding ribosomal
                      proteins, mitochondrial-encoded RNAs and long non-coding
                      RNAs. Previous works have reported the existence of
                      transcription factors (TFs) in the axon. Here, we detect a
                      set of TFs specific to the axon and indicative of their
                      active participation in transcriptional regulation. To
                      investigate transcripts and pathways essential for central
                      motor neuron (MN) degeneration and maintenance we analysed
                      kinesin family member 1C (KIF1C)-knockout (KO) CNs,
                      modelling hereditary spastic paraplegia, a disorder
                      associated with prominent length-dependent degeneration of
                      central MN axons. We found that several key factors crucial
                      for survival and health were absent in KIF1C-KO axons,
                      highlighting a possible role of these also in other
                      neurodegenerative diseases. Taken together, this study
                      underscores the utility of microfluidic devices in studying
                      compartment-specific transcriptomics in human neuronal
                      models and reveals complex molecular dynamics of axonal
                      biology. The impact of KIF1C on the axonal transcriptome not
                      only deepens our understanding of MN diseases but also
                      presents a promising avenue for exploration of
                      compartment-specific disease mechanisms.},
      keywords     = {Induced Pluripotent Stem Cells: metabolism / Induced
                      Pluripotent Stem Cells: cytology / Axons: metabolism / Motor
                      Neurons: metabolism / Motor Neurons: pathology / Animals /
                      Mice / Transcriptome / Humans / Gene Expression Profiling /
                      Transcription Factors: metabolism / Kinesins: genetics /
                      Kinesins: metabolism / Nerve Degeneration: genetics / Nerve
                      Degeneration: metabolism / axonal transcriptomics (Other) /
                      axonal transport (Other) / iPSC-derived neurons (Other) /
                      kinesin (Other) / neurons (Other) / transcription factors
                      (Other) / Transcription Factors (NLM Chemicals) / Kinesins
                      (NLM Chemicals)},
      cin          = {AG Hauser / AG Schöls},
      ddc          = {570},
      cid          = {I:(DE-2719)1210016 / I:(DE-2719)5000005},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1098/rsob.250101},
      url          = {https://pub.dzne.de/record/279124},
}