Kuijk, Ewart, Jager, Myrthe, van der Roest, Bastiaan, Locati, Mauro D., Van Hoeck, Arne, Korzelius, Jerome, Janssen, Roel, Besselink, Nicolle, Boymans, Sander, van Boxtel, Ruben, and others. (2020) The mutational impact of culturing human pluripotent and adult stem cells. Nature Communications, 11 (1). E-ISSN 2041-1723. (doi:10.1038/s41467-020-16323-4) (KAR id:81480)
PDF
Publisher pdf
Language: English |
||
Download (1MB)
Preview
|
|
|
This file may not be suitable for user of assistive technology. Request an accessible format. |
||
Official URL http://dx.doi.org/10.1038/s41467-020-16323-4 |
Abstract
Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies.
Item Type: | Article |
---|---|
DOI/Identification number: | 10.1038/s41467-020-16323-4 |
Uncontrolled keywords: | stem cells, organoid culture, mutation frequency, oxidative stress |
Subjects: |
Q Science > QH Natural history > QH426 Genetics Q Science > QH Natural history > QH581.2 Cell Biology Q Science > QL Zoology |
Divisions: | Faculties > Sciences > School of Biosciences > Cell & Developmental Biology Group |
Depositing User: | Jerome Korzelius |
Date Deposited: | 01 Jun 2020 13:59 UTC |
Last Modified: | 03 Jun 2020 03:12 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/81480 (The current URI for this page, for reference purposes) |
Korzelius, Jerome: | ![]() |
- Export to:
- RefWorks
- EPrints3 XML
- BibTeX
- CSV
- Depositors only (login required):