Evolution from adherent to suspension: systems biology of HEK293 cell line development
Journal article, 2020
The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.
Author
Magdalena Malm
Royal Institute of Technology (KTH)
Rasool Saghaleyni
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Magnus Lundqvist
Royal Institute of Technology (KTH)
Marco Giudici
Royal Institute of Technology (KTH)
Veronique Chotteau
Royal Institute of Technology (KTH)
Ray Field
AstraZeneca AB
GammaDelta Therapeutics Ltd
Paul G. Varley
AstraZeneca AB
Kymab Limited
Diane Hatton
AstraZeneca AB
Luigi Grassi
AstraZeneca AB
Thomas Svensson
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Jens B Nielsen
Technical University of Denmark (DTU)
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
J. Rockberg
Royal Institute of Technology (KTH)
Scientific Reports
2045-2322 (ISSN) 20452322 (eISSN)
Vol. 10 1 18996Subject Categories
Cell Biology
Cell and Molecular Biology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DOI
10.1038/s41598-020-76137-8
PubMed
33149219