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Series GSE118308 Query DataSets for GSE118308
Status Public on Sep 27, 2018
Title Epigenetic extinction of fetal programming promotes leukemia stem cell activity
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Acute leukemias are aggressive malignancies of developmentally arrested hematopoietic progenitors. We sought here to explore the possibility that changes in hematopoietic stem/progenitor cells during aging might alter the biology of leukemias arising from this tissue compartment. Using a mouse model of acute T-cell leukemia, we found that leukemias generated from fetal liver (FL) and adult bone marrow (BM) differed dramatically in their leukemia stem cell activity with FL leukemias showing markedly reduced serial transplantability as compared to BM leukemias. We present evidence that this difference is due to NOTCH1-driven autocrine IGF1 signaling which is active in FL cells, but restrained in BM cells by EZH2-dependent H3K27 trimethylation. Further, we confirmed this mechanism is operative in human disease, and show that enforced IGF1 signaling effectively limits leukemia stem cell activity. These findings demonstrate that resurrecting dormant fetal programs in adult cells may represent an alternate therapeutic approach in human cancer.
 
Overall design Examination of H3K27me3 in 2 mouse cell types
 
Contributor(s) Giambra V, Gusscott S, Gracias D, Song R, Lam S, Panelli P, Tyshchenko K, Jenkins C, Hoofd C, Lorzadeh A, Carles A, Hirst M, Eaves C, Weng AP
Citation(s) 30269902
Submission date Aug 08, 2018
Last update date Mar 19, 2019
Contact name Martin Hirst
E-mail(s) hirst@msl.ubc.ca
Phone 604-827-4505
Organization name University of British Columbia
Department Microbiology and Immunology
Street address 2125 East Mall
City Vancouver
State/province British Columbia
ZIP/Postal code V6T 1Z4
Country Canada
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM3324568 H3K27me3_mouse_bone_marrow_N1dE
GSM3324569 H3K27me3_mouse_fetal_liver_N1dE
GSM3324570 Input_mouse_bone_marrow_N1dE
Relations
BioProject PRJNA485143
SRA SRP156763

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
GSE118308_RAW.tar 1.2 Mb (http)(custom) TAR (of BROADPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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