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Series GSE133755 Query DataSets for GSE133755
Status Public on Jul 27, 2020
Title In vitro restoration of Friedreich's Ataxia defect with novel Cas9-edited hiPSC-derived Dorsal Root Ganglion-like Organoids (DRGOs) and Microfluidic System
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Friedreich's ataxia (FRDA) is an autosomal-recessive neurodegenerative and cardiac disorder which occurs when transcription of the frataxin (FXN) gene is silenced due to the expansion of GAA·TTC repeats in intron 1 of the same gene, leading loss of the essential mitochondrial protein frataxin with several impairment in iron metabolism and respiration, primarily affects the sensory DRG neurons. A major limitation in the study of FRDA is the lack of robust animal and cellular models. To fill this gap, this study presents a novel 3D protocol to generate dorsal root ganglia-like organoids (DRGOs) from human iPSCs in which to model Friedreich's ataxia. DRGOs show a robust expression pattern of peripheral markers, are electro-physiologically active and out-perform peripheral sensory neurons generated with a traditional 2D protocol. Furthermore, when co-cultured with human stretch receptor intrafusal muscle fibers, DRGOs contact their peripheral target and form an in vitro muscle spindle. DRGOs generated from FRDA patient-derived iPSCs recapitulate several aspects of FRDA pathology including reduced expression of FXN and TCA-cycle components and mitochondrial fragmentation. We present also the recovery of this pathological signs, achieved by a new CRISPR-Cas9 mediated deletion of the GAA·TTC tract along with the majority of the affected intron. FRDA patient edited DRGOs with the long deletion boast normalized markers of oxidative stress, as well as recovered mitochondrial defect, particularly in the axonal compartment.
Overall design 3x Dorsal Root Ganglia Organoids
Contributor(s) Mazzara PG, Massimino L, Broccoli V
Citation(s) 32826895, 36140168
Submission date Jul 03, 2019
Last update date Oct 04, 2022
Contact name Luca Massimino
Phone 3389039500
Organization name Ospedale San Raffaele
Department Gastroenterology
Street address Via Olgettina, 58
City Milano
State/province MI
ZIP/Postal code 20100
Country Italy
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (3)
GSM3926661 DRGO-CTRL-1
GSM3926662 DRGO-CTRL-2
GSM3926663 DRGO-CTRL-3
BioProject PRJNA552467
SRA SRP212865

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Supplementary file Size Download File type/resource
GSE133755_RAW.tar 950.0 Kb (http)(custom) TAR (of TAB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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