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| Status |
Public on May 26, 2020 |
| Title |
Expression of RUNX1-ETO Rapidly Alters the Chromatin Landscape and Growth of Early Human Myeloid Precursor Cells (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acute myeloid leukemia is a hematopoietic malignancy caused by recurrent mutations in genes encoding transcriptional, epigenetic and/or signaling regulators. The t(8;21) translocation generates the aberrant transcription factor RUNX1-ETO, whose expression can be detected in utero but is insufficient to cause overt disease. Although patients harboring cells with the t(8;21) translocation have acquired additional mutations and show extensive epigenetic reprogramming, the effects directly and solely attributable to RUNX1-ETO expression are unclear. To address this question, we used a human embryonic stem cell differentiation system capable of forming definitive human myeloid progenitor cells to express RUNX1-ETO in an inducible fashion. Induction of RUNX1-ETO causes extensive chromatin reprogramming by interfering with RUNX1 binding, blocks differentiation and arrests cellular growth, whereby growth arrest is reversible following RUNX1-ETO removal. Single cell gene expression analyses show that RUNX1-ETO induction alters the differentiation of a defined sub-population of progenitors, indicating that oncoprotein-mediated transcriptional reprogramming is highly target cell-specific.
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| Overall design |
RNA-Seq of human embryonic stem cells that have undergone hematopoietic differentiation. These cells contain a doxycycline-inducible RUNX1-ETO construct. Cells were treated with 0, 3, 5 or 10 ng/ml of dox prior to sequencing. All experiments were conducted in triplicate.
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| Contributor(s) |
Keane P, Nafria M, Ng E, Stanley E, Elefanty A, Bonifer C |
| Citation(s) |
32460028 |
| Submission date |
Sep 18, 2019 |
| Last update date |
Aug 25, 2020 |
| Contact name |
Peter Keane |
| E-mail(s) |
p.keane@bham.ac.uk
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| Organization name |
University of Birmingham
|
| Department |
Institute for Cancer and Genomic Sciences
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| Street address |
Vincent Drive
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| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE137673 |
Expression of RUNX1-ETO Rapidly Alters the Chromatin Landscape and Growth of Early Human Myeloid Precursor Cells |
|
| Relations |
| BioProject |
PRJNA566185 |
| SRA |
SRP222352 |
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