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Series GSE160224 Query DataSets for GSE160224
Status Public on Feb 04, 2021
Title Efficient manipulation of gene dosage in human iPSCs using CRISPR/Cas9 nickases
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer’s disease. However, there is no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we describe a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. We first generate a Cas9 nickase variant with broader protospacer-adjacent motif specificity to expand the targetability of double-nicking–mediated genome editing. As a proof-of-concept study, we examine the gene dosage effects on Alzheimer’s disease pathogenesis patient-derived iPSC line that carries three copies of APP (amyloid precursor protein). This method enables the rapid and simultaneous generation of iPSC lines with monoallelic, biallelic, or triallelic knockout of APP. The cortical neurons generated from isogenically corrected iPSCs exhibit gene dosage-dependent correction of disease-associated phenotypes of amyloid-beta secretion and Tau hyperphosphorylation. Thus, the rapid generation of iPSCs with different gene dosages using the method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.
Overall design RNA-sequencing of neurons derived from nondemented control (NDC), APP duplication (APP) and isogenically-corrected (Iso) iPSC lines
Contributor(s) Ye T, Duan Y, Tsang HW, Xu H, Chen Y, Cao H, Chen Y, Fu AK, Ip NY
Citation(s) 33580208
Submission date Oct 27, 2020
Last update date Feb 15, 2021
Contact name Nancy Y. Ip
Organization name Hong Kong University of Science and Technology
Street address Room 6313, Academic Building The Hong Kong University of Science and Technology Clear Water Bay, Kowloon
City Hong Kong
ZIP/Postal code 000000
Country China
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (9)
GSM4869291 NDC rep1
GSM4869292 NDC rep2
GSM4869293 NDC rep3
BioProject PRJNA672661
SRA SRP288814

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
GSE160224_RAW.tar 2.2 Mb (http)(custom) TAR (of CSV)
GSE160224_Raw_gene_counts_matrix.csv.gz 687.5 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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