UC scientists develop CRISPR-engineered stem cell models

Recently, researchers at the University of California San Diego School of Medicine used genetically engineered human pluripotent stem cells to create a new type of cancer model for studying, in vivo, how glioblastoma develops and changes over time.

Co-senior author Dr. Frank B. Furnari said: "We have developed a CRISPR-engineered stem cell model with tumor-associated gene mutations in glioblastoma. Cells carrying these mutations essentially have all the characteristics of patient-derived tumors, including extrachromosomal DNA amplification."

In an article recently published in Nature Communications, the researchers used CRISPR editing technology to introduce targeted mutations in an otherwise normal genome, thereby creating genetic variants that can promote tumor development. The engineered tumor cells behaved very similarly to grade 4 glioma in terms of behavior, pathology, transcriptomic signatures and the evolution of genetic mutations.

Co-senior author Gene W. Yeo said: "The addition of single-cell RNA sequencing and computational tools allows us to truly assess tumor heterogeneity in vivo through big data analysis."

Existing mouse models can be used to test anticancer drugs against specific types of mutations, but cannot be applied to all tumor types. The authors believe this new modeling system provides a new platform for standardized research on tumor biology and evolution.

Yeo said: "We can now predict through testing which mutations really drive tumor initiation, and how they become invasive." Furnari said the model well mimics the previously observed phenomenon of tumor cell heterogeneity, making it the best choice for screening tumor evolution characteristics and seeking treatment options based on genetics. (Source: 生物谷. Information source: Stem cells, CRISPR and gene sequencing technology are basis of new brain cancer model. Original source: Koga, T et al. Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells. Nat Commun 11, 550 (2020). doi.org/10.1038/s41467-020-14312-1)