In this work, we developed a CRISPR interference/activation-based system to manipulate the expression level of single transporter genes. Using pooled screening, we can then systematically interrogate the contribution of all transporters to nutrient import/export in environments ranging from standard culture media to tumors. We applied this platform to identify the transporters of amino acids in leukemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition. While investigating the role of transporters in cystine starved cells, we uncovered a role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumours and found that levels of glucose and amino acids can restrain proliferation in that environment. This study establishes a framework for systematically identifying critical cellular nutrient transporters, characterizing their function and exploring how the tumor microenvironment impacts cancer metabolism.
Check out the final version of the paper here: https://www.nature.com/articles/s41556-024-01402-1
