Generation of a genetically-modified induced pluripotent stem cell line harboring an oncogenic gene variant KRAS

Alexandra Viktoria Busley1, Mandy Kleinsorge2, Lukas Cyganek1

  • 1Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Germany; Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany & Hertha Sponer College, Göttingen, Germany.

Stem Cell Research
|April 30, 2023
PubMed

Insights

Researchers created a human induced pluripotent stem cell (iPSC) line with the KRAS G12V mutation. This KRAS G12V iPSC line aids in studying cancer signaling pathways and developing new cancer drugs.

Area of Science:

  • Molecular Biology
  • Genetics
  • Stem Cell Biology

Background:

  • Activating KRAS codon 12 variants cause RAS-MAPK and PI3K-AKT pathway hyperactivity.
  • These variants are implicated in the development of various carcinomas.

Purpose of the Study:

  • To generate a human induced pluripotent stem cell (iPSC) line harboring the KRAS p.G12V variant.
  • To establish a platform for studying oncogenic KRAS-induced signaling and its physiological impact.
  • To enable drug and toxicity screenings for novel chemotherapeutic agents.

Main Methods:

  • CRISPR/Cas9 gene editing technology was employed.
  • Generation of a human iPSC line with the specific KRAS G12V mutation.

Main Results:

  • Successfully established a human iPSC line carrying the KRAS G12V oncogenic variant.
  • The iPSC line facilitates investigation of oncogenic KRAS-driven signaling.
  • The cell line provides a model for studying effects on iPSC-derived cell types and tissues.

Conclusions:

  • The KRAS G12V iPSC line is a valuable tool for understanding oncogenic KRAS.
  • This platform supports the identification of new chemotherapeutic drugs through screening.
  • Enables research into cancer signaling and potential therapeutic interventions.