2021 is off to a great start! I’m very excited to share my new study at @CellStemCell on using surface antigen-guided CRISPR screens to identify genes that regulate myeloid leukemia differentiation.
Here's my first tweetorial! 1. Here, we used two innovative genetic screen approaches, a cell surface-based genome-wide and single-cell (ECCITE-seq) CRISPR screens to identify regulators of AML differentiation.
2. We focused our efforts on the mRNA decay factor, ZFP36L2 which demonstrated a strong dependency in human myeloid leukemia cell lines (@CancerDepMap).
3. Knockout of ZFP36L2 resulted in several upregulated genes associated with myeloid differentiation. Together with ZFP36L2 eCLIP (thanks to @bio_eclipse), we found that this RNA-binding protein interacts with the 3’UTR of specific myeloid maturation mRNAs.
4. Moreover, we identified a selective enhancer nearby ZFP36L2 and perturbation of this enh-ZFP36L2 using CRISPRi led to changes in the differentiated state of AML cells.
5. Lastly, special thanks to @psmibert and Eleni for the technical help on using ECCITE-seq! Also, this work would not be possible without the amazing team of @iannisaifantis1 and the #aifantislab crew!
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