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Wellcome-MRC Cambridge Stem Cell Institute

 
A Tale of Two States

Researchers from Peter Rugg-Gunn’s lab (Cambridge Stem Cell Institute Affiliate PI, Babraham Institute)  and colleagues at the Karolinska Institute have identified a set of molecular ‘flags’ that are present on the surface of human embryonic stem cells. Embryonic stem cells are cells that have the potential to differentiate into any cell in the body.  Through recognition of the different molecular flags, researchers can now accurately track and investigate stem cells as they change into their destination cell type. This approach has revealed new insights into the timing and coordination of the changes in gene activity as cells are reprogrammed from one state to another.

These exciting findings could open up new ways for scientists to improve the efficiency of cell reprogramming, and to identify specific cell types during this process. These are important steps towards future applications in regenerative medicine, which would require the use of stem cells to create specialised cells to restore normal tissue function after injury or disease.

Human embryonic stem cells can exist in two different states that are termed naïve (the ground state) and primed (the state before differentiation into a specialised cell). The two states differ in the set of genes they express, the pattern of modifications to their DNA, and whether an X chromosome in female cells is silenced or not. The two cell types can transition back and forth, but do so with very low efficiency.  Using the newly discovered ‘flags’ to monitor the cells as they transition back and forth could provide important new insights into how cellular differences are established as stem cells undergo specialisation, and also during the early stages of human development.

Until now, researchers have lacked the right tools to tell naïve and primed stem cells apart when they are mixed together, and this has hindered the investigation of the cells as they transition from one state to another.  It will be exciting to see how these new ‘flags’ are used by scientists to advance our understanding of stem cells, with the hope of ultimately developing new treatments for human disease.

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Publication reference

Collier and Panula et al. (2017) Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States. Cell Stem Cell  

DOI: http://dx.doi.org/10.1016/j.stem.2017.02.014

 

Image description

Use of the immunofluorescent microscopy visualisation technique reveals the presence of specific proteins in ‘naïve’ human embryonic stem cells. The stem cells have been coloured to represent the different proteins detected in this study. Image credit: Dr. Sarita Panula, Karolinska Institute.