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Series GSE58123 Query DataSets for GSE58123
Status Public on Apr 10, 2015
Title Modeling Familial Cancer with iPSC Approaches
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In vitro modeling of human disease has recently become feasible with the adoption of induced pluripotent stem cell (iPSC) technology. Here, we established patient-derived iPSCs from an Li-Fraumeni Syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS). Several members of this family carried a heterozygous p53(G245D) mutation and presented with a broad spectrum of tumors including OS. Osteoblasts (OBs) differentiated from iPSC-derived mesenchymal stem cells (MSCs) recapitulated OS features including defective osteoblastic differentiation (OB differentiation) as well as tumorigenic ability. Systematic analyses revealed that the expression of genes enriched in LFS-derived OBs strongly correlated with decreased time to tumor recurrence and poor patient survival. In silico cytogenetic region enrichment analysis (CREA) demonstrated that LFS-derived OBs do not have genomic rearrangements and hence are a particularly valuable tool for elucidating early oncogenic events prior to the accumulation of secondary alterations. LFS OBs exhibited impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration of H19 expression in LFS OBs facilitated osteogenic differentiation and repressed tumorigenic potential. By integrating human imprinted gene network (IGN) and functional genomic analyses, we found that H19-mediates suppression of LFS-associated OS through the IGN component DECORIN (DCN). Downregulation of DCN impairs H19-mediated osteogenic differentiation and tumor suppression. In summary, these findings demonstrate the feasibility of studying inherited human cancer syndromes with iPSCs and also provide molecular insights into the role of the IGN in p53 mutation-mediated tumorigenesis.
Overall design mRNAseq profiling during mesenchymal stem cell differentiation to osteoblasts.
Contributor(s) Chang B, Lee D, Lemischka IR
Citation(s) 25860607
Submission date May 30, 2014
Last update date May 15, 2019
Contact name Betty Chang
Organization name Mount Sinai School of Medicine
Street address 1425 Madison Ave
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (14)
GSM1401369 LFS1-A_day0
GSM1401370 LFS1-A_day7
GSM1401371 LFS1-A_day14
BioProject PRJNA249062
SRA SRP042597

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
GSE58123_LFSMSCDerivedTumor.txt.gz 250.8 Kb (ftp)(http) TXT
GSE58123_MSCtoOB_FPKM.txt.gz 908.1 Kb (ftp)(http) TXT
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Processed data are available on Series record

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