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Series GSE24901 Query DataSets for GSE24901
Status Public on Oct 26, 2010
Title Therapeutic globin expression in thalassemia patient induced pluripotent stem cells from genomic safe harbors
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The advent of human induced pluripotent stem (iPS) cells enables for the first time the derivation of unlimited numbers of patient-specific stem cells and holds great promise for regenerative medicine. However, realizing the full potential of iPS cells requires robust, precise and safe strategies for their genetic modification. Safe human iPS cell engineering is especially needed for therapeutic applications, as stem cell-based therapies that rely on randomly integrated transgenes pose oncogenic risks. Here we describe a strategy to genetically modify iPS cells from patients with beta-thalassemia in a potentially clinically relevant manner. Our approach is based on the identification and selection of “safe harbor” sites for transgene expression in the human genome. We show that thalassemia patient iPS cell clones harboring a transgene can be isolated and screened according to chromosomal position. We next demonstrate that iPS cell clones that meet our “safe harbor” criteria resist silencing and allow for therapeutic levels of beta-globin expression upon erythroid differentiation without perturbation of neighboring gene expression. Combined bioinformatics and functional analyses thus provide a robust and dependable approach for achieving desirable levels of transgene expression from selected chromosomal loci. This approach may be broadly applicable to introducing therapeutic or suicide genes into patient specific iPS cells for use in cell therapy.
 
Overall design iPS cell clones were derived from beta-thalassemia patients. A single copy of beta-globin transgene cis-linked to locus control region (LCR) elements and an excisable Neo-eGFP transcription unit were inserted into these cell clones. beta-globin expression was induced by erythroid differentiation.
 
Contributor(s) Papapetrou EP, Lee G, Malani N, Setty M, Riviere I, Tirunagari LM, Kadota K, Roth SL, Giardina P, Viale A, Leslie C, Bushman FD, Studer L, Sadelain M
Citation(s) 21151124
Submission date Oct 25, 2010
Last update date Aug 16, 2018
Contact name Manu Setty
E-mail(s) msetty@fredhutch.org
Organization name Fred Hutchinson Cancer Center
Department Basic Sciences Division
Street address 1100 Fairview Ave N
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
Samples (30)
GSM612313 Thal1.52_A
GSM612314 Thal1.52_B
GSM612315 Thal1.52_C
Relations
BioProject PRJNA132087

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
GSE24901_RAW.tar 6.2 Mb (http)(custom) TAR
GSE24901_non-normalized_data.txt.gz 8.5 Mb (ftp)(http) TXT
Processed data included within Sample table

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