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Series GSE127743 Query DataSets for GSE127743
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
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.
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.
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
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Submission date Mar 02, 2019
Last update date Jan 19, 2023
Contact name Gene Yeo
Organization name UCSD
Street address 2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (4)
GSM3638031 sgElavl1 rep1
GSM3638032 sgElavl1 rep2
GSM3638033 sgControl rep1
BioProject PRJNA525226
SRA SRP187330

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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
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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