Activin/Nodal signalling in stem cells
Ludovic Vallier and Siim Pauklin publish a review in Development describing the function of Activin/Nodal/TGFbeta signalling in stem cells and diseases.
Human Pluripotent Stem Cells (hPSCs) are derived from embryo at the blastocyst stage (human Embryonic Stem Cells or hESCs) or generated from reprogrammed somatic cells (human Induced Pluripotent Stem Cells or hIPSCs). These pluripotent cells can self-renew indefinitely in vitro while maintaining their capacity to differentiate into a broad number of cell types. As such, hPSCs could allow the production of an infinite quantity of cells with a clinical interest, thus making them uniquely interesting for regenerative medicine, disease modelling, and drug screening.
hPSCs rely on Activin/Nodal and FGF to maintain their pluripotent status. Inhibition of Activin/Nodal signaling induces neuroectoderm differentiation while being necessary for endoderm specification. Smad2/3, the Activin/Nodal signaling effectors, achieve this apparent contradictory function by controlling divergent transcriptional networks in hPSCs and during their differentiation. Thus, activity of Activin/Nodal must be tightly regulated by a diversity of co-factors including epigenetic modifiers and cell cycle regulators.
This review describes how these principles could be transferred to adult stem cells and to diseases such as cancer.
Pauklin S, Vallier L. Activin/Nodal signalling in stem cells. Development. PMID:25670788