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Series GSE248128 Query DataSets for GSE248128
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
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.
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
Contributor(s) Sonsalla G, Masserdotti G, Prokisch H
Citation(s) 38266647
Submission date Nov 17, 2023
Last update date Apr 17, 2024
Contact name Giacomo Masserdotti
Organization name Helmholtz Zentrum
Department ISF
Street address Groshaderner Strasse 9
City Planegg-Martinstied
ZIP/Postal code 82152
Country Germany
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM7906200 control,DsRed,no treatment,CMO305,Day 20
GSM7906201 control,DsRed,AMG,CMO306,Day 20
GSM7906202 control,Ngn2,no treatment,CMO307,Day 20
This SubSeries is part of SuperSeries:
GSE248129 Unfolded protein Response is a major hurdle in direct neuronal reprogramming of human astrocytes
BioProject PRJNA1041808

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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