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Status |
Public on Jan 24, 2024 |
Title |
Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes [scRNA-seq day 20] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead to neurological disorders and contribute to the onset of age-related diseases. Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but almost nothing is known about the impact of mitochondrial dysfunction in human cell direct reprogramming. Here we explore the defects and how to improve the neuronal reprogramming of iPSC-derived astrocytes carrying mutations in NDUFS4 gene, important for Complex I and associated to Leigh Sydrome. This led to the identification of the unfolded protein response as a major hurdle in the direct neuronal conversion of not only patient, but also control astrocytes and fibroblasts. Our data highlight mitochondria-ER stress-mediated inhibition of translation as a key hurdle in direct neuronal reprogramming, emphasizing how disease modelling using patient cells can contribute to unravel novel pathways in human glia cell reprogramming.
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Overall design |
pAstros were transduced with control or Ngn2-expressing retrovirus. 2DPT, media was replaced with differentiation media in absence of presence of AMG; 20DPT, DsRed-positive cells were sorted, barcoded with CMOs and analyzed by scRNAseq via 10XGenoics platform
*************************************************************** Raw data will be deposited in GHGA when the database is available ***************************************************************
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Contributor(s) |
Sonsalla G, Masserdotti G, Prokisch H |
Citation(s) |
38266647 |
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Submission date |
Nov 17, 2023 |
Last update date |
Apr 17, 2024 |
Contact name |
Giacomo Masserdotti |
E-mail(s) |
giacomo.masserdotti@helmholtz-munich.de
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Organization name |
Helmholtz Zentrum
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Department |
ISF
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Street address |
Groshaderner Strasse 9
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City |
Planegg-Martinstied |
ZIP/Postal code |
82152 |
Country |
Germany |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (8)
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GSM7906200 |
control,DsRed,no treatment,CMO305,Day 20 |
GSM7906201 |
control,DsRed,AMG,CMO306,Day 20 |
GSM7906202 |
control,Ngn2,no treatment,CMO307,Day 20 |
GSM7906203 |
control,Ngn2,AMG,CMO308,Day 20 |
GSM7906204 |
patient,DsRed,no treatment,CMO309,Day 20 |
GSM7906205 |
patient,DsRed,AMG,CMO310,Day 20 |
GSM7906206 |
patient,Ngn2,no treatment,CMO311,Day 20 |
GSM7906207 |
patient,Ngn2,AMG,CMO312,Day 20 |
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This SubSeries is part of SuperSeries: |
GSE248129 |
Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes |
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Relations |
BioProject |
PRJNA1041808 |
Supplementary file |
Size |
Download |
File type/resource |
GSE248128_Rep1_raw_feature_bc_matrix.tar.gz |
151.0 Mb |
(ftp)(http) |
TAR |
GSE248128_Rep2_raw_feature_bc_matrix.tar.gz |
151.0 Mb |
(ftp)(http) |
TAR |
Raw data not provided for this record |
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