Equipe Labellisee La Ligue Contre Le Cancer

Paris, France

Equipe Labellisee La Ligue Contre Le Cancer

Paris, France
SEARCH FILTERS
Time filter
Source Type

Betous R.,Equipe Labellisee La Ligue Contre Le Cancer | Betous R.,French Institute of Health and Medical Research | Betous R.,University Paul Sabatier | Renoud M.-L.,University Paul Sabatier | And 13 more authors.
Stem Cells Translational Medicine | Year: 2017

Adipose-derived stem cells (ADSCs) have led to growing interest in cell-based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA-seq) that culture of ADSCs under atmospheric oxygen concentration leads to misex-pression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress-associated transformation, as occurs in neoplastic tissues. © 2016 The Authors.

Loading Equipe Labellisee La Ligue Contre Le Cancer collaborators
Loading Equipe Labellisee La Ligue Contre Le Cancer collaborators