Abstract: In certain example embodiments, the invention provides a method of generating an ex vivo cell-based system comprising dissociating an original tissue sample obtained from a subject into a single cell population; determining an in vivo phenotype of the tissue sample by conducting single-cell RNA analysis on a first portion of the single cells; establishing an ex vivo cell-based system from a second portion of the single cells; and culturing the ex vivo cell-based system in a medium or conditions selected to maintain the in vivo phenotype. In some embodiments, the original tissue sample is a tumor tissue sample, such as a pancreatic ductal adenocarcinoma (PDAC) tumor sample.