You are hereFebruary 17, 2018 | ESCs/iPSCs
Stem Cells: License to be Pluripotent!
Review of “Rapid DNA replication origin licensing protects stem cell pluripotency” from eLife by Stuart P. Atkinson
We require a license to drive, a license to marry, a certain James Bond even needs a license to kill (!) and now, new research from the laboratory of Jeanette Gowen Cook (University of North Carolina, USA) suggests that proper “licensing” also ensures that stem cells remain pluripotent !
In this new study, licensing refers to origin licensing, the process of helicase loading onto DNA for genome duplication purposes during the G1 phase of the cell cycle. Interestingly, studies have indicated that a short G1 phase is a hallmark of pluripotent stem cells (PSCs) [2, 3], only lengthening during differentiation . The author’s new study, published in eLife, now employs single-cell flow cytometry to describe how rapid origin licensing represents an important means to maintain the pluripotent state.
Initial analyses by Matson et al. confirmed that the embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) under study indeed displayed naturally short G1 phases. Subsequent single-cell flow cytometric assays linked this shorter G1 phase to the more rapid loading of minichromosome maintenance (MCM) helicase complexes when compared to differentiated cells with longer G1 phases (neural progenitor cells and retinal pigmented epithelial cells). Rapid licensing occurred thanks to the accumulation of the Cdt1 MCM loading protein via upregulated mRNA expression and specific re-accumulation of the Cdt1 protein in the preceding G2 phase.
Interestingly, assessment of the early stages of PSC differentiation indicated the existence of developmental control of helicase loading, as licensing slowed with the lengthening of the G1 phase. Additionally, the authors furthered the link between origin licensing/MCM loading and pluripotency by establishing that artificial inhibition of MCM loading actually lengthened G1 phase and accelerated PSC differentiation.
The authors hope that this study into origin licensing in PSCs and the discovery of a link between cell differentiation and DNA replication will further direct investigations into the early stages of developmental biology, cancer initiation and progression, and regenerative medicine.
To check out more details on how stem cells get their license to be pluripotent, stay tuned to the Stem Cells Portal!
- Matson JP, Dumitru R, Coryell P, et al., Rapid DNA replication origin licensing protects stem cell pluripotency. eLife 2017;6:e30473.
- Soufi A and Dalton S, Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming. Development 2016;143:4301-4311.
- Kareta MS, Sage J, and Wernig M, Crosstalk between stem cell and cell cycle machineries. Curr Opin Cell Biol 2015;37:68-74.
- Calder A, Roth-Albin I, Bhatia S, et al., Lengthened G1 phase indicates differentiation status in human embryonic stem cells. Stem Cells Dev 2013;22:279-95.