We developed this protocol while trying to isolate single-nuclei from frozen liposarcoma tissue. We tested this protocol on a variety of PDX's. For fattier tissues, we use a modified protocol based on a different kit. Thanks to Dr. Luciano Martelotto for his assistance and tips on the first section. This protocol is based on prior work: \u2018Frankenstein\u2019 protocol, Nuclei Isolation Kit: Nuclei EZ Prep, and Minute\u2122 Total Protein Extraction Kit for Adipose Tissues\/Cultured Adipocytes.