
iPSC 유래 피질 신경세포의 축삭과 세포체 간 전사체 프로파일이 뚜렷하게 구분되며, KIF1C 결손이 축삭 전사체에 광범위한 변화를 유발함


coremsg

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 (RNA-seq) approach, using microfluidic devices, to generate high-quality axonal transcriptomes from iPSC-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, ribosomal proteins (RPs), mitochondrial-encoded RNAs, and long non-coding RNAs (lncRNAs). Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a subset of previously unreported 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 analyzed KIF1C-knockout (KO) CNs, modeling hereditary spastic paraplegia (HSP), 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.

### Competing Interest Statement

The authors have declared no competing interest.

*   ALS
    :   Amyotrophic lateral sclerosis
    APC
    :   Adenomatous-polyposis-coli-protein
    BDNF
    :   Brain derived neurotrophic factor
    bp
    :   basepairs
    BP
    :   Biological process
    CC
    :   Cellular component
    CMT
    :   Charcot-Marie-Tooth
    CN
    :   Cortical neuron
    CNS
    :   Central nervous system
    DAI
    :   Day after induction
    DRG
    :   Dorsal root ganglia
    EJC
    :   Exon junction complex
    GDNF
    :   Glial cell line-derived neurotrophic factor
    GO
    :   Gene ontology
    GWAS
    :   Genome-wide association studies
    HSP
    :   Hereditary spastic paraplegia
    HD
    :   Huntington disease
    IPSC
    :   Induced pluripotent stem cell
    KIF1C
    :   Kinesin family member 1 C
    KO
    :   knockout
    MF
    :   Molecular function
    MN
    :   Motor neuron
    mt
    :   Mitochondrial
    NGF
    :   Nerve growth factor
    QC
    :   Quality control
    PC
    :   Principal component
    PCA
    :   Principal component analysis
    RP
    :   Ribosomal protein
    SMA
    :   Spinal muscular atrophy
    SPG58
    :   Hereditary spastic paraplegia type 58
    STMN
    :   Stathmin
    TF
    :   Transcription Factor
    TPM
    :   Transcripts per million
    RNA-seq
    :   RNA-sequencing
    WT
    :   Wild-type

Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration

ipsc-유래-피질-신경세포의-축삭-전사체-분석을-통한-운동신경세포-퇴행의-통찰


iPSC 유래 피질 신경세포의 축삭 전사체 분석을 통한 운동신경세포 퇴행의 통찰
