The mutational impact of culturing human pluripotent and adult stem cells.
Nat Commun
; 11(1): 2493, 2020 05 19.
Article
en En
| MEDLINE
| ID: mdl-32427826
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
/
Células Madre Adultas
/
Células Madre Pluripotentes Inducidas
/
Mutación
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2020
Tipo del documento:
Article