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GSE276986

GSE GEO
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Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]

Organism: Homo sapiens
Platform: GPL24676
Samples: 22
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Sep 11 2024
Last Updated: Feb 18 2025
Status: Public on Feb 18 2025
Contact: Kevin,,Rhine (University of Arizona)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1159892

Summary

Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged healthy donors directly into neurons, which retained their aging markers. Here we show that aged neurons are broadly depleted of RNA-binding proteins, especially spliceosome components. Intriguingly, splicing proteins – like the dementia and ALS-associated protein TDP-43 – mislocalize to the cytoplasm in aged neurons, which leads to widespread alternative splicing. Cytoplasmic spliceosome components typically are recruited to stress granules, but aged neurons suffer from chronic stress that prevents this sequestration. We link chronic stress to the malfunctioning ubiquitylation machinery, poor HSP90α chaperone activity, and the failure to respond to new stress events. Together our data demonstrates that aging-linked deterioration of RNA biology is a key driver of poor resiliency in aged neurons.

Overall Design

NGS RNA-seq of isogenic transdifferentiated and iPSC-derived neurons before, immediately after, and 24 h after acute stress treatment with 0.5 mM sodium arsenite; deep sequencing was also performed for pre-stress conditions

Analysis (1 step)

View Data Processing
Processing steps for GSE276986
  1. RNA-Seq data was processed using the NF-Core architecture, which compiles several RNA-seq processing steps into a single executable command

Supplementary Files (2)

GSE276986_featurecounts_deepRNA-Seq.csv.gz Download
GSE276986_featurecounts_recoveryRNA-Seq.txt.gz Download
GEO Samples (22)
GSM8510723 GSM8510724 GSM8510725 GSM8510726 GSM8510727 GSM8510728 GSM8510729 GSM8510730 GSM8510731 GSM8510732 GSM8510733 GSM8510734 GSM8510735 GSM8510736 GSM8510737 GSM8510738 GSM8510739 GSM8510740 GSM8510741 GSM8510742 GSM8510743 GSM8510744

SRA Experiments (22) and Runs (22)

Total: 29079 MB
SRX26061326 SRP532164 RNA-Seq SINGLE
GSM8510723: iPSC-DerivedNeurons_deep_1; Homo sapiens; RNA-Seq
Sample: SRS22630847
BioProject: PRJNA1159892
BioSample: SAMN43587314
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639534 49987191 10097412582 2971.27 Ngn2_deep_1.fastq, SRR30639534, SRR30639534.lite SRA
SRX26061327 SRP532164 RNA-Seq SINGLE
GSM8510724: iPSC-DerivedNeurons_deep_2; Homo sapiens; RNA-Seq
Sample: SRS22630843
BioProject: PRJNA1159892
BioSample: SAMN43587313
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639533 11046813 2231456226 680.91 Ngn2_deep_2.fastq, SRR30639533, SRR30639533.lite SRA
SRX26061328 SRP532164 RNA-Seq SINGLE
GSM8510725: TransdifferentiatedNeurons_deep_1; Homo sapiens; RNA-Seq
Sample: SRS22630844
BioProject: PRJNA1159892
BioSample: SAMN43587312
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639532 3415894 690010588 207.82 NK_deep_1.fastq, SRR30639532, SRR30639532.lite SRA
SRX26061329 SRP532164 RNA-Seq SINGLE
GSM8510726: TransdifferentiatedNeurons_deep_2; Homo sapiens; RNA-Seq
Sample: SRS22630845
BioProject: PRJNA1159892
BioSample: SAMN43587311
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639531 52692414 10643867628 3173.17 NK_deep_2.fastq, SRR30639531, SRR30639531.lite SRA
SRX26061330 SRP532164 RNA-Seq PAIRED
GSM8510727: iPSC-DerivedNeurons_0h_recovery_1; Homo sapiens; RNA-Seq
Sample: SRS22630849
BioProject: PRJNA1159892
BioSample: SAMN43587310
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639530 5605401 571750902 193.63 NGN_0_A_S21_L001_R1_001.fastq.gz, NGN_0_A_S21_L001_R2_001.fastq.gz, S… SRA
SRX26061331 SRP532164 RNA-Seq PAIRED
GSM8510728: iPSC-DerivedNeurons_0h_recovery_2; Homo sapiens; RNA-Seq
Sample: SRS22630846
BioProject: PRJNA1159892
BioSample: SAMN43587309
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639529 19237858 1962261516 650.64 NGN_0_B_S22_L001_R1_001.fastq.gz, NGN_0_B_S22_L001_R2_001.fastq.gz, S… SRA
SRX26061332 SRP532164 RNA-Seq PAIRED
GSM8510729: iPSC-DerivedNeurons_0h_recovery_3; Homo sapiens; RNA-Seq
Sample: SRS22630852
BioProject: PRJNA1159892
BioSample: SAMN43587308
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639528 45217771 4612212642 1515.17 NGN_0_C_S23_L001_R1_001.fastq.gz, NGN_0_C_S23_L001_R2_001.fastq.gz, S… SRA
SRX26061333 SRP532164 RNA-Seq PAIRED
GSM8510730: iPSC-DerivedNeurons_24h_recovery_1; Homo sapiens; RNA-Seq
Sample: SRS22630848
BioProject: PRJNA1159892
BioSample: SAMN43587307
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639527 87244136 8898901872 2919.51 NGN_24_A_S18_L001_R1_001.fastq.gz, NGN_24_A_S18_L001_R2_001.fastq.gz,… SRA
SRX26061334 SRP532164 RNA-Seq PAIRED
GSM8510731: iPSC-DerivedNeurons_24h_recovery_2; Homo sapiens; RNA-Seq
Sample: SRS22630850
BioProject: PRJNA1159892
BioSample: SAMN43587306
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639526 18131146 1849376892 611.85 NGN_24_B_S19_L001_R1_001.fastq.gz, NGN_24_B_S19_L001_R2_001.fastq.gz,… SRA
SRX26061335 SRP532164 RNA-Seq PAIRED
GSM8510732: iPSC-DerivedNeurons_24h_recovery_3; Homo sapiens; RNA-Seq
Sample: SRS22630857
BioProject: PRJNA1159892
BioSample: SAMN43587305
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639525 3816205 389252910 130.47 NGN_24_C_S20_L001_R1_001.fastq.gz, NGN_24_C_S20_L001_R2_001.fastq.gz,… SRA
SRX26061336 SRP532164 RNA-Seq PAIRED
GSM8510733: iPSC-DerivedNeurons_pre-stress_1; Homo sapiens; RNA-Seq
Sample: SRS22630851
BioProject: PRJNA1159892
BioSample: SAMN43587304
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639524 198513443 20248371186 6601.48 SRR30639524.lite, SRR30639524, NGN_U_A_S24_L001_R2_001.fastq.gz, NGN_… SRA
SRX26061337 SRP532164 RNA-Seq PAIRED
GSM8510734: iPSC-DerivedNeurons_pre-stress_2; Homo sapiens; RNA-Seq
Sample: SRS22630853
BioProject: PRJNA1159892
BioSample: SAMN43587303
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639523 64113926 6539620452 2144.55 NGN_U_B_S25_L001_R1_001.fastq.gz, NGN_U_B_S25_L001_R2_001.fastq.gz, S… SRA
SRX26061338 SRP532164 RNA-Seq PAIRED
GSM8510735: iPSC-DerivedNeurons_pre-stress_3; Homo sapiens; RNA-Seq
Sample: SRS22630854
BioProject: PRJNA1159892
BioSample: SAMN43587302
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: iPSC-derived cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639522 53162152 5422539504 1781.91 NGN_U_C_S26_L001_R1_001.fastq.gz, NGN_U_C_S26_L001_R2_001.fastq.gz, S… SRA
SRX26061339 SRP532164 RNA-Seq PAIRED
GSM8510736: TransdifferentiatedNeurons_0h_recovery_1; Homo sapiens; RNA-Seq
Sample: SRS22630860
BioProject: PRJNA1159892
BioSample: SAMN43587301
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639521 9023585 920405670 308.38 NK_0_A_S12_L001_R1_001.fastq.gz, NK_0_A_S12_L001_R2_001.fastq.gz, SRR… SRA
SRX26061340 SRP532164 RNA-Seq PAIRED
GSM8510737: TransdifferentiatedNeurons_0h_recovery_2; Homo sapiens; RNA-Seq
Sample: SRS22630855
BioProject: PRJNA1159892
BioSample: SAMN43587300
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639520 12036574 1227730548 412.28 NK_0_B_S13_L001_R1_001.fastq.gz, NK_0_B_S13_L001_R2_001.fastq.gz, SRR… SRA
SRX26061341 SRP532164 RNA-Seq PAIRED
GSM8510738: TransdifferentiatedNeurons_0h_recovery_3; Homo sapiens; RNA-Seq
Sample: SRS22630861
BioProject: PRJNA1159892
BioSample: SAMN43587299
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639519 14830935 1512755370 500.38 NK_0_C_S14_L001_R1_001.fastq.gz, NK_0_C_S14_L001_R2_001.fastq.gz, SRR… SRA
SRX26061342 SRP532164 RNA-Seq PAIRED
GSM8510739: TransdifferentiatedNeurons_24h_recovery_1; Homo sapiens; RNA-Seq
Sample: SRS22630856
BioProject: PRJNA1159892
BioSample: SAMN43587298
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639518 13424933 1369343166 456.22 NK_24_A_S9_L001_R1_001.fastq.gz, NK_24_A_S9_L001_R2_001.fastq.gz, SRR… SRA
SRX26061343 SRP532164 RNA-Seq PAIRED
GSM8510740: TransdifferentiatedNeurons_24h_recovery_2; Homo sapiens; RNA-Seq
Sample: SRS22630858
BioProject: PRJNA1159892
BioSample: SAMN43587297
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639517 21320889 2174730678 720.07 NK_24_B_S10_L001_R1_001.fastq.gz, NK_24_B_S10_L001_R2_001.fastq.gz, S… SRA
SRX26061344 SRP532164 RNA-Seq PAIRED
GSM8510741: TransdifferentiatedNeurons_24h_recovery_3; Homo sapiens; RNA-Seq
Sample: SRS22630859
BioProject: PRJNA1159892
BioSample: SAMN43587296
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: 0.5 mM sodium arsenite for 1 h, recovery for 24 h
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639516 21132269 2155491438 717.8 NK_24_C_S11_L001_R1_001.fastq.gz, NK_24_C_S11_L001_R2_001.fastq.gz, S… SRA
SRX26061345 SRP532164 RNA-Seq PAIRED
GSM8510742: TransdifferentiatedNeurons_pre-stress_1; Homo sapiens; RNA-Seq
Sample: SRS22630862
BioProject: PRJNA1159892
BioSample: SAMN43587295
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639515 34990647 3569045994 1176.16 NK_U_A_S15_L001_R1_001.fastq.gz, NK_U_A_S15_L001_R2_001.fastq.gz, SRR… SRA
SRX26061346 SRP532164 RNA-Seq PAIRED
GSM8510743: TransdifferentiatedNeurons_pre-stress_2; Homo sapiens; RNA-Seq
Sample: SRS22630864
BioProject: PRJNA1159892
BioSample: SAMN43587294
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639514 26506517 2703664734 889.57 NK_U_B_S16_L001_R1_001.fastq.gz, NK_U_B_S16_L001_R2_001.fastq.gz, SRR… SRA
SRX26061347 SRP532164 RNA-Seq PAIRED
GSM8510744: TransdifferentiatedNeurons_pre-stress_3; Homo sapiens; RNA-Seq
Sample: SRS22630863
BioProject: PRJNA1159892
BioSample: SAMN43587293
Platform: ILLUMINA
Instrument: NextSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Kin17ALS1
cell line: Kin17ALS1
cell type: Transdifferentiated cortical neurons
treatment: n/a
geo_loc_name: missing
collection_date: missing
Original files (1)
Kin17ALS1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR30639513 9297187 948313074 315.54 NK_U_C_S17_L001_R1_001.fastq.gz, NK_U_C_S17_L001_R2_001.fastq.gz, SRR… SRA

Linked Publications (1)

Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.
Nature neuroscience · 2025

Data Files (22)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— NGN_0_A_S21_L001_R1_001.fastq.gz RNA-Seq 193.6 MB link
— NGN_0_B_S22_L001_R1_001.fastq.gz RNA-Seq 650.6 MB link
— NGN_0_C_S23_L001_R1_001.fastq.gz RNA-Seq 1.5 GB link
— NGN_24_A_S18_L001_R1_001.fastq.gz RNA-Seq 2.9 GB link
— NGN_24_B_S19_L001_R1_001.fastq.gz RNA-Seq 611.8 MB link
— NGN_24_C_S20_L001_R1_001.fastq.gz RNA-Seq 130.5 MB link
— Ngn2_deep_1.fastq RNA-Seq 2.9 GB link
— Ngn2_deep_2.fastq RNA-Seq 680.9 MB link
— NGN_U_B_S25_L001_R1_001.fastq.gz RNA-Seq 2.1 GB link
— NGN_U_C_S26_L001_R1_001.fastq.gz RNA-Seq 1.7 GB link
— NK_0_A_S12_L001_R1_001.fastq.gz RNA-Seq 308.4 MB link
— NK_0_B_S13_L001_R1_001.fastq.gz RNA-Seq 412.3 MB link
— NK_0_C_S14_L001_R1_001.fastq.gz RNA-Seq 500.4 MB link
— NK_24_A_S9_L001_R1_001.fastq.gz RNA-Seq 456.2 MB link
— NK_24_B_S10_L001_R1_001.fastq.gz RNA-Seq 720.1 MB link
— NK_24_C_S11_L001_R1_001.fastq.gz RNA-Seq 717.8 MB link
— NK_deep_1.fastq RNA-Seq 207.8 MB link
— NK_deep_2.fastq RNA-Seq 3.1 GB link
— NK_U_A_S15_L001_R1_001.fastq.gz RNA-Seq 1.1 GB link
— NK_U_B_S16_L001_R1_001.fastq.gz RNA-Seq 889.6 MB link
— NK_U_C_S17_L001_R1_001.fastq.gz RNA-Seq 315.5 MB link
— SRR30639524.lite RNA-Seq 6.4 GB link