Evolution from adherent to suspension: systems biology of HEK293 cell line development
Artikel i vetenskaplig tidskrift, 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.
Författare
Magdalena Malm
Kungliga Tekniska Högskolan (KTH)
Rasool Saghaleyni
Chalmers, Biologi och bioteknik, Systembiologi
Magnus Lundqvist
Kungliga Tekniska Högskolan (KTH)
Marco Giudici
Kungliga Tekniska Högskolan (KTH)
Veronique Chotteau
Kungliga Tekniska Högskolan (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, Biologi och bioteknik, Systembiologi
Jens B Nielsen
Danmarks Tekniske Universitet (DTU)
Chalmers, Biologi och bioteknik, Systembiologi
J. Rockberg
Kungliga Tekniska Högskolan (KTH)
Scientific Reports
2045-2322 (ISSN) 20452322 (eISSN)
Vol. 10 1 18996Ämneskategorier
Cellbiologi
Cell- och molekylärbiologi
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1038/s41598-020-76137-8
PubMed
33149219