Marius Wernig is the scientist who first directly converted fibroblast into Induced Neurons (iN) with the ectopic expression of only three factors. In this talk, he argumented that this process seems to be more fast and efficient than the canonical reprogramming to pluripotency. By investigating the functional role of the transcription factors involved at single cell resolution, he founds that there are discrepancy on the binding of the key reprogramming players to the target genes. Indeed, while Ascl1, the key player in iN formation, appears to bind its physiological target through the interaction with nucleosomal DNA, the main “reprogram to pluripotency” factors as Oct4 and Sox2 bind ectopic genomic regions that are typically not bound in ES cells. Thus, the dynamic and specificity of the interaction of the key factors with chromatin determine the efficiency of the reprogramming process.
During senescence, cells undergo a proliferative arrest that seems to induce a tumorigenic effect on the neighbouring cells through secretion of specific molecules. The identification of senescence-related genes reveals that some of these are also stem cell-related genes. In vivo transplantation of senescent cells suggests that their tumor formation role could be played by altering the endogenous stem cell fate.
Austin Smith is probably the investigator that is constantly giving more indications on how to capture the ground state of pluripotent stem cells. His work is based on the characterization of the ground state of pluripotent stem cell lines cultured with different conditions. Embryonic stem cells (ESCs) could be cultured in vitro as an homogenous population. Despite they are used as a general model of pluripotent cells, it has to be take into account that their gene expression profile match with a specific subset of cells that, during the embryonic development in vivo, is present in a specific space and time. Austin Smith define a new culture condition of human ESCs through which it is possible to capture a ground state quite similar to the once of human embryo tissues and to mouse ES cell lines but different from the current human ES cell lines characterized.
CRG Symposium 2014