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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 18, 2023 |
| Title |
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNA binding protein (RBP)-directed post-transcriptional control of stem cell fate represents an underexplored mechanism driving hematopoietic stemness and transformation. We show that a unique set of RBPs are specifically enriched in leukemic stem cells (LSCs) of human primary acute myeloid leukemia (AML) but repressed in normal hematopoietic stem cells. Using an in vivo CRISPR-Cas9-mediated screening approach, we identify 33 key RBPs specifically essential for LSC-mediated MLL-AF9/NrasG12D AML. Knock-down/genetic ablation of the hit RBP Elavl1 in genetically distinct leukemias significantly reduced LSC numbers, and hampered leukemic engraftment. In human AML we show impairment of LSC-driven in vivo leukemic reconstitution and selective depletion of AML progenitors upon ELAVL1 targeting, highlighting the potential clinical importance of our findings. Profiling of the leukemic ELAVL1-mRNA interactome revealed hematopoietic differentiation, RNA splicing and mitochondrial metabolism as major pathways impacted by ELAVL1. Altogether, this work demonstrates that Elavl1 and other RBPs are critical regulators of LSC-survival and self-renewal.
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| Overall design |
2x sgNTC, 2x sgELAVL1; Cells were transduced with lentiviral-packaged sgRNA targeting Elavl1 and, as control, Ano9. 72 hours following transduction live 7AAD- GFP+ cells were isolated.
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| Contributor(s) |
de Rooij LP, Vujovic A, Loganathan S, Yee BA, Chahi AK, Chan DC, Tajik A, Zandi S, Wong N, Aigner S, Dick JE, Minden MD, Schramek D, Yeo GW, Hope KJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Mar 02, 2019 |
| Last update date |
Jan 19, 2023 |
| Contact name |
Gene Yeo |
| E-mail(s) |
geneyeo@ucsd.edu
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| Organization name |
UCSD
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| Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA525226 |
| SRA |
SRP187330 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127743_RAW.tar |
630.4 Mb |
(http)(custom) |
TAR (of BW) |
| GSE127743_counts.RN2c.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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