Chromatin decondensation and nuclear softening accompany Nanog downregulation in ESCs

We used biophysical techniques to study nuclear mechanics and higher-order chromatin organisation in embryonic stem cells. We investigated two states: a naïve and pre-committed state (i.e. the state that immediately precedes commitment of the embryonic stem cells). We found that cells in a pre-committed state have a significantly softer nucleus and more globally decondensed chromatin. We hypothesise that this combination of physical factors relates to the plasticity of the pre-committed stem cell in responding to chemical and physical cues from its environment.

Biophys J. 2012 Nov 21;103(10):2060-70.

Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cell

(A) We used optical trapping to stretch the nuclei of embryonic stem (ES) cells to test their softness. We looked at nuclear mechanics with decreasing levels of Nanog expression, and found that nuclear mechanics correlates well with Nanog expression (we validated this using NanogGFP cells). (B) We then used fluorescence recovery after photobleaching on ES cells transfected with H2BRFP, and showed that H2B diffuses more quickly in pre-committed cells (low Nanog expressing), which we interpret to mean that chromatin is more globally decondensed in pre-committed cells than ES cells in a naïve state (high Nanog expressing). (Credit: Kevin Chalut)

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