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Series GSE67282 Query DataSets for GSE67282
Status Public on Dec 01, 2015
Title Establishment of tractable human iPSC-based models for the study and targeting of glioma initiation (ChIP-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Gliomas can originate upon transformation of adult Neural Progenitor Cells (NPCs) to Tumor Initiating Cells (TICs). Studies on human Glioma TICs (GTICs) have focused on the use of primary tumors from which GTICs could be isolated. Therefore investigations on the driver events underlying NPC transformation and human glioma initiation remain limited to the use of human embryonic material. Here we report on the development of strategies for the modeling of human gliomagenesis based on the use of human induced Pluripotent Stem Cells (hiPSCs). Transformation of hiPSC-derived NPCs (iNPCs) by defined genetic alterations led to the establishment of tractable human GTIC models suitable for studying the early steps of gliomagenesis as well as for screening studies. Dysregulation of PI3K, MAPK and p53 signaling in iNPCs led to the acquisition of functional GTIC properties. In vivo transplantation led to the formation of highly aggressive, infiltrative and heterogeneous tumors upon limited dilutions and secondary transplantation, faithfully recapitulating gliomagenesis. Metabolic modulation by chemical approaches compromised GTIC viability. Pilot screening of 101 anti-cancer compounds identified 3 molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results demonstrate the potential of hiPSCs for the functional testing of putative driver mutations underlying human tumorigenesis and pave new avenues for the development of personalized cancer therapeutics.
 
Overall design Five samples were subjected to ChIP-Seq for both Sox2 and H3K4me3, wild-type neural progenitor cells, neural progenitor cells with P53 knockdown, neural progenitor cells with P53 knockdown and inhibition of the PI3K and MAPK signaling pathways, neural progenitor cells with the inhibition of the PI3K and MAPK signaling pathways, and Glioma Stem Cells (Glioma Tumor Initiating Cells).
 
Contributor(s) Morey RE, Laurent L, Sancho-Martinez I, Belmonte JI
Citation(s) 26899176
Submission date Mar 25, 2015
Last update date May 15, 2019
Contact name Robert E Morey
E-mail(s) robmoreyucsd@gmail.com, remorey@eng.ucsd.edu
Organization name UCSD
Department Reproductive Medicine
Lab Laurent/Parast
Street address 2880 Torrey Pines Scenic Dr
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (10)
GSM1643794 Sample1_GNS-Sox2
GSM1643795 Sample2_NPCwt-Sox2
GSM1643796 Sample3_NPC_4F-Sox2
This SubSeries is part of SuperSeries:
GSE67286 Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
Relations
BioProject PRJNA279411
SRA SRP056546

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