Home > In process > Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS. > print

001     285016
005     20260203103022.0
024 7 _ |a 10.1016/j.nbd.2026.107268
|2 doi
024 7 _ |a pmid:41525886
|2 pmid
024 7 _ |a 0969-9961
|2 ISSN
024 7 _ |a 1095-953X
|2 ISSN
037 _ _ |a DZNE-2026-00142
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Zimyanin, Vitaly
|0 P:(DE-HGF)0
|b 0
|e First author
245 _ _ |a Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS.
260 _ _ |a [Amsterdam]
|c 2026
|b Elsevier
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1770110856_10795
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Mutations in FUSED IN SARCOMA (FUS) cause juvenile-onset amyotrophic lateral sclerosis (ALS). Early pathogenesis of FUS-ALS involves impaired transcription and splicing, DNA damage response, and axonal degeneration. However, the molecular pathophysiology and the link between somatic and axonal phenotypes are still poorly understood. We evaluated whether compartment-specific transcriptome differences could distinguish and drive early axonal degeneration. We used iPSC-derived motor neurons (MNs) coupled with microfluidic approaches to generate RNA-sequencing profiles from axonal and somatodendritic compartments. We demonstrate that the axonal transcriptome is unique and distinct, with RNA metabolism, extracellular secretion, and matrix disassembly pathways particularly enriched in distal axonal compartments. FUS mutation leads to changes in distinct pathways that were clustered in only a few distinct protein-protein interaction (PPI) networks. Somatodendritic changes upon FUS mutation include WNT signaling, mitochondrial, extracellular matrix (ECM)-, and synapse-related functions. In contrast, analysis of the axonal transcriptome in mutant MNs centers on the PLK1 pathway, mitochondrial gene expression, and regulation of inflammation. Comparison to CLIP-seq data revealed a significant enrichment for PLK1 and DNA replication pathways in axons. PLK1 upregulation did not activate cell-cycle re-entry but contributed to mutant MNs survival, and its inhibition increased neuronal cell death. We propose that upregulation of PLK1 represents an early event in the pathogenesis of ALS and could act in response to DNA damage, mitochondrial damage, and immune response activation in the affected cells. Additionally, downregulation of ECM pathways in the somatodendritic compartment and axons could explain strongly compromised dynamics of axonal outgrowth. Overall, we provide a novel valuable resource of the potential targets and affected processes changed in the specific compartments of FUS-ALS motor neurons.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Amyotrophic lateral sclerosis
|2 Other
650 _ 7 |a Axon degeneration
|2 Other
650 _ 7 |a Axonal outgrowth
|2 Other
650 _ 7 |a Axonal transcriptome
|2 Other
650 _ 7 |a Cell cycle
|2 Other
650 _ 7 |a DNA damage, PLK1
|2 Other
650 _ 7 |a ECM
|2 Other
650 _ 7 |a Induced pluripotent stem cells
|2 Other
650 _ 7 |a RNA sequencing
|2 Other
650 _ 7 |a RNA-Binding Protein FUS
|2 NLM Chemicals
650 _ 7 |a Cell Cycle Proteins
|2 NLM Chemicals
650 _ 7 |a FUS protein, human
|2 NLM Chemicals
650 _ 2 |a Motor Neurons: metabolism
|2 MeSH
650 _ 2 |a Motor Neurons: pathology
|2 MeSH
650 _ 2 |a RNA-Binding Protein FUS: genetics
|2 MeSH
650 _ 2 |a RNA-Binding Protein FUS: metabolism
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: pathology
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Extracellular Matrix: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cell Cycle Proteins: metabolism
|2 MeSH
650 _ 2 |a Cell Cycle Proteins: genetics
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Signal Transduction: physiology
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
700 1 _ |a Dash, Banaja P
|b 1
700 1 _ |a Simolka, Theresa
|b 2
700 1 _ |a Glaß, Hannes
|b 3
700 1 _ |a Pal, Arun
|b 4
700 1 _ |a Haidle, Felix
|b 5
700 1 _ |a Zarnack, Kathi
|b 6
700 1 _ |a Verma, Riya
|b 7
700 1 _ |a Khatri, Vivek
|b 8
700 1 _ |a Deppmann, Christopher
|b 9
700 1 _ |a Zunder, Eli
|b 10
700 1 _ |a Müller-McNicoll, Michaela
|b 11
700 1 _ |a Redemann, Stefanie
|b 12
700 1 _ |a Hermann, Andreas
|0 P:(DE-2719)2811732
|b 13
|e Last author
|u dzne
773 _ _ |a 10.1016/j.nbd.2026.107268
|g Vol. 219, p. 107268 -
|0 PERI:(DE-600)1471408-5
|p 107268
|t Neurobiology of disease
|v 219
|y 2026
|x 0969-9961
856 4 _ |u https://pub.dzne.de/record/285016/files/DZNE-2026-00142.pdf
|y Restricted
856 4 _ |u https://pub.dzne.de/record/285016/files/DZNE-2026-00142.pdf?subformat=pdfa
|x pdfa
|y Restricted
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-HGF)0
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 13
|6 P:(DE-2719)2811732
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2025-08-21T14:53:16Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2025-08-21T14:53:16Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Anonymous peer review
|d 2025-08-21T14:53:16Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-11-11
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-11-11
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NEUROBIOL DIS : 2022
|d 2025-11-11
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2025-11-11
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2025-11-11
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b NEUROBIOL DIS : 2022
|d 2025-11-11
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2025-11-11
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2025-11-11
920 1 _ |0 I:(DE-2719)1511100
|k AG Hermann
|l Translational Neurodegeneration
|x 0
980 _ _ |a journal
980 _ _ |a EDITORS
980 _ _ |a VDBINPRINT
980 _ _ |a I:(DE-2719)1511100
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21