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Science Papers Describe Signature of Epithelial-Mesenchymal Plasticity, MiRNA System to Purify iPSCs

By examining single-cell RNA sequencing data for a range of different cancers, a pair of researchers from the University of Ottawa has identified molecular features associated with epithelial-mesenchymal plasticity (EMP), a hallmark of tumor progression. The ability of cells to interconvert between epithelial and mesenchymal phenotypes has been broadly associated with metastasis, chemoresistance, and immunosuppression in cancer. In the study, which appears in Science Advances, the scientists analyzed scRNA-seq data from 266 tumors across eight tumor types including colorectal, gastric, lung, nasopharyngeal, squamous cell carcinoma, ovarian, pancreatic ductal adenocarcinoma, and breast to identify coordinated expression programs consistent with intratumoral EMP. While the overall composition of the programs was highly variable, the researchers derived a set of well-conserved genes to serve as a general EMP signature. They used this signature to query pan-cancer data in The Cancer Genome Atlas, revealing that EMP was associated with reduced progression-free intervals and a more immunosuppressive tumor microenvironment. Computational approaches further inferred regulatory features of EMP across hundreds of samples, highlighting that diversity may emerge from common regulatory mechanisms that can be inferred and used to rationalize therapeutic strategies.

A novel, microRNA-based system for the purification of human induced pluripotent stem cells (iPSCs) is described by a Kyoto University team in Science Advances this week. Although iPSCs hold great promise as cell resources for drug discovery and regenerative medicine, iPSC-derived differentiated cells are often heterogenous and require purification using a flow cytometer, which is both expensive and time consuming to perform on a large scale. Given that miRNAs can be used as cell selection markers since their activity differs between cell types, the researchers developed miRNA-responsive on-and-off switch mRNAs that can be used for cell purification. The on-switch contains a miRNA-target sequence after the polyadenylate tail, triggering translational activation by sensing the target miRNA, they say. "By designing RNA-only circuits with miRNA-on and -off switch mRNAs that encode a lethal ribonuclease, Barnase, and its inhibitor, Barstar, we efficiently purified specific cell types, including human iPSCs and differentiated cardiomyocytes, without flow cytometry," the researchers add.