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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
Examination of H3K27me3 in 2 mouse cell types
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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 |
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Submission date |
Aug 08, 2018 |
Last update date |
Mar 19, 2019 |
Contact name |
Martin Hirst |
E-mail(s) |
hirst@msl.ubc.ca
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Phone |
604-827-4505
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Organization name |
University of British Columbia
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Department |
Microbiology and Immunology
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Street address |
2125 East Mall
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City |
Vancouver |
State/province |
British Columbia |
ZIP/Postal code |
V6T 1Z4 |
Country |
Canada |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA485143 |
SRA |
SRP156763 |
Supplementary file |
Size |
Download |
File type/resource |
GSE118308_RAW.tar |
1.2 Mb |
(http)(custom) |
TAR (of BROADPEAK) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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