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Series GSE228254 Query DataSets for GSE228254
Status Public on May 22, 2024
Title Mono and biallelic inactivation of Huntingtin gene in patient-specific iPS cells reveal HTT roles in striatal development and in neuronal functions impaired in Huntington’s disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Mutations in the Huntingtin (HTT) gene cause Huntington disease (HD), a neurodegenerative disorder. While HTT is known to be involved, as a scaffold protein, in several cellular functions, its normal and pathogenic functions during the development of the human forebrain remain poorly understood. To investigate the roles of wild-type and mutant HTT alleles during human neural and striatal development we inactivated HTT alleles in a series of isogenic clones of a human induced pluripotent stem cell (iPSC) line derived from a patient with HD. We show that the loss of wild-type, mutant, or both HTT isoforms did not affect the pluripotency of iPSCs or their transition into neural cells. However, we observed that HTT loss caused division impairments in forebrain neuro-epithelial cells. Moreover, HTT-/- derivatives displayed impaired maturation of medium spiny neurons (MSNs) particularly in the acquisition of DARPP32 expression, a key functional marker of MSNs. Finally, we discovered that MSNs and cortical neurons derived from HTT-/- clones exhibited higher levels of baseline DNA damage and lower BDNF axonal transport, two cellular dysfunctions previously described in HD neurons.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for Mono and biallelic inactivation of Huntingtin gene in patient-specific iPS cells
 
Contributor(s) Louessard M, Cailleret M, Jarrige M, Bigarreau J, Lenoir S, Saudou F, Deglon N, Perrier AL
Citation(s) 38427495
Submission date Mar 27, 2023
Last update date May 22, 2024
Contact name MARGOT JARRIGE
E-mail(s) mjarrige@istem.fr
Phone +33169908529
Organization name I-Stem/INSERM U861
Street address 28, Rue Henri Desbruères
City Corbeil-Essonnes
ZIP/Postal code 91100
Country France
 
Platforms (1)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (31)
GSM7117783 IonXpress_011_R_2019_10_11_14_46_22_NGS55_libQ195
GSM7117784 IonXpress_012_R_2019_10_11_14_46_22_NGS55_libQ196
GSM7117785 IonXpress_013_R_2019_10_10_17_02_28_NGS56_libQ197
Relations
BioProject PRJNA949142

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE228254_Reads_count_Normalised.txt.gz 2.0 Mb (ftp)(http) TXT
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Processed data are available on Series record
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