Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells

Open access
Date
2018-06Type
- Journal Article
Citations
Cited 11 times in
Web of Science
Cited 11 times in
Scopus
ETH Bibliography
yes
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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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000274995Publication status
publishedExternal links
Journal / series
Stem Cell ReportsVolume
Pages / Article No.
Publisher
Cell PressSubject
2i; Gsk3; Mek; embryonic stem cells; pluripotency; Nanog; cell heterogeneity; continuous time-lapse imaging; single-cell tracking; cell fateOrganisational unit
03992 - Schroeder, Timm / Schroeder, Timm
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Show all metadata
Citations
Cited 11 times in
Web of Science
Cited 11 times in
Scopus
ETH Bibliography
yes
Altmetrics