000279124 001__ 279124 000279124 005__ 20250708100956.0 000279124 0247_ $$2doi$$a10.1098/rsob.250101 000279124 037__ $$aDZNE-2025-00684 000279124 041__ $$aEnglish 000279124 082__ $$a570 000279124 1001_ $$0P:(DE-2719)9002275$$aXu, Jishu$$b0 000279124 245__ $$aUnravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration 000279124 260__ $$aLondon$$bRoyal Society Publishing$$c2025 000279124 3367_ $$2DRIVER$$aarticle 000279124 3367_ $$2DataCite$$aOutput Types/Journal article 000279124 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1751891780_24568 000279124 3367_ $$2BibTeX$$aARTICLE 000279124 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000279124 3367_ $$00$$2EndNote$$aJournal Article 000279124 520__ $$aNeuronal 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. 000279124 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000279124 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x1 000279124 588__ $$aDataset connected to DataCite 000279124 650_7 $$2Other$$aaxonal transcriptomics 000279124 650_7 $$2Other$$aaxonal transport 000279124 650_7 $$2Other$$aiPSC-derived neurons 000279124 650_7 $$2Other$$akinesin 000279124 650_7 $$2Other$$aneurons 000279124 650_7 $$2Other$$atranscription factors 000279124 650_7 $$2NLM Chemicals$$aTranscription Factors 000279124 650_7 $$0EC 3.6.4.4$$2NLM Chemicals$$aKinesins 000279124 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism 000279124 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: cytology 000279124 650_2 $$2MeSH$$aAxons: metabolism 000279124 650_2 $$2MeSH$$aMotor Neurons: metabolism 000279124 650_2 $$2MeSH$$aMotor Neurons: pathology 000279124 650_2 $$2MeSH$$aAnimals 000279124 650_2 $$2MeSH$$aMice 000279124 650_2 $$2MeSH$$aTranscriptome 000279124 650_2 $$2MeSH$$aHumans 000279124 650_2 $$2MeSH$$aGene Expression Profiling 000279124 650_2 $$2MeSH$$aTranscription Factors: metabolism 000279124 650_2 $$2MeSH$$aKinesins: genetics 000279124 650_2 $$2MeSH$$aKinesins: metabolism 000279124 650_2 $$2MeSH$$aNerve Degeneration: genetics 000279124 650_2 $$2MeSH$$aNerve Degeneration: metabolism 000279124 7001_ $$0P:(DE-HGF)0$$aHörner, Michaela$$b1 000279124 7001_ $$0P:(DE-2719)2812101$$aNagel, Maike$$b2 000279124 7001_ $$0P:(DE-HGF)0$$aPerhat, Perwin$$b3 000279124 7001_ $$0P:(DE-2719)9002166$$aKorneck, Milena$$b4 000279124 7001_ $$0P:(DE-HGF)0$$aNoß, Marvin$$b5 000279124 7001_ $$0P:(DE-2719)2810998$$aHauser, Stefan$$b6$$udzne 000279124 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b7$$udzne 000279124 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