How cells change their identity to become a different cell type and the route they follow to reach their final form is a fundamental unanswered question at the heart of developmental biology.
In research published today in Cell Stem Cell, Cambridge scientists reveal, for the first time, that cells can actually follow a range of distinct molecular routes in order to reach the same final cell type, demonstrating a surprising flexibility in cell decision making during cell fate change.
“Our new research used cellular reprogramming to model how a given cell type changes its identity to become another cell type. The results showed that this could be done in many different ways” explained Dr Jose Silva, leader of the study at the Wellcome – MRC Cambridge Stem Cell Institute. “This was a surprising result because it was previously thought that cell fate change followed a particular order of molecular events.”
The one thing that all the routes had in common was the activation and maintenance of Oct4 expression, an important protein that controls which genes are switched on and off in early embryo development.
“Fine tuning of Oct4 seems to play an important role in the routes stem cells follow during cellular decision making” said Dr Hannah Stuart, lead author on the new paper “Oct4 was not only required but sufficient to induce reprogramming of somatic cells, such as embryonic skin cells, back into a stem cell identity where cells regained the competence to become all of the cell types of the body.”
The research team now plan to build on this work to understand the potential parallels to other cell fate decisions such as during the creation of cell types with clinical relevance from embryonic stem cells.
The support of the Wellcome, MRC, Bloodwise, CRUK and NIH are gratefully acknowledged by the team.
Publication details:
Distinct molecular trajectories converge to induce naïve pluripotency. H Stuart, G Stirparo, T Lohoff, L Bates, M Kinoshita, C Lim, E Sousa, K Maskalenka, A Radzisheuskaya, A Malcolm, M Alves, R Lloyd, S Nestorowa, P Humphreys, W Mansfield, W Reik, P Bertone, J Nichols, B Göttgens and J Silva is published in Cell Stem Cell. DOI:10.1016/j.stem.2019.07.009