Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells
Hastreiter S, Skylaki S, Loeffler D, Reimann A, Hilsenbeck O, Hoppe PS, Coutu DL, Kokkaliaris KD, Schwarzfischer M, Anastassiadis K, Theis FJ, Schroeder T (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 11
Pages Range: 58-69
Journal Issue: 1
DOI: 10.1016/j.stemcr.2018.04.019
Abstract
Embryonic stem cells (ESCs) display heterogeneous expression of pluripotency factors such as Nanog when cultured with serum and leukemia inhibitory factor (LIF). In contrast, dual inhibition of the signaling kinases GSK3 and MEK (2i) converts ESC cultures into a state with more uniform and high Nanog expression. However, it is so far unclear whether 2i acts through an inductive or selective mechanism. Here, we use continuous time-lapse imaging to quantify the dynamics of death, proliferation, and Nanog expression in mouse ESCs after 2i addition. We show that 2i has a dual effect: it both leads to increased cell death of Nanog low ESCs (selective effect) and induces and maintains high Nanog levels (inductive effect) in single ESCs. Genetic manipulation further showed that presence of NANOG protein is important for cell viability in 2i medium. This demonstrates complex Nanog-dependent effects of 2i treatment on ESC cultures.
Involved external institutions
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
Switzerland (CH)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
How to cite
APA:
Hastreiter, S., Skylaki, S., Loeffler, D., Reimann, A., Hilsenbeck, O., Hoppe, P.S.,... Schroeder, T. (2018). Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells. Stem Cell Reports, 11(1), 58-69. https://doi.org/10.1016/j.stemcr.2018.04.019
MLA:
Hastreiter, Simon, et al. "Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells." Stem Cell Reports 11.1 (2018): 58-69.
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