title: Dedifferentiation of foetal CNS stem cells to mesendoderm-like cells through an EMT process.
abstract: Tissue-specific stem cells are considered to have a limited differentiation potential. Recently, this notion was challenged by reports that showed a broader differentiation potential of neural stem cells, in vitro and in vivo, although the molecular mechanisms that regulate plasticity of neural stem cells are unknown. Here, we report that neural stem cells derived from mouse embryonic cortex respond to Lif and serum in vitro and undergo epithelial to mesenchymal transition (EMT)-mediated dedifferentiation process within 48 h, together with transient upregulation of pluripotency markers and, more notably, upregulation of mesendoderm genes, Brachyury (T) and Sox17. These induced putative mesendoderm cells were injected into early gastrulating chick embryos, which revealed that they integrated more efficiently into mesoderm and endoderm lineages compared to non-induced cells. We also found that TGFβ and Jak/Stat pathways are necessary but not sufficient for the induction of mesendodermal phenotype in neural stem cells. These results provide insights into the regulation of plasticity of neural stem cells through EMT. Dissecting the regulatory pathways involved in these processes may help to gain control over cell fate decisions.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge, United Kingdom. sb681@cam.ac.uk
authors.forename: Suzan
authors.initials: S
authors.lastname: Ber
authors.forename: Caroline
authors.initials: C
authors.lastname: Lee
authors.forename: Octavian
authors.initials: O
authors.lastname: Voiculescu
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005326:Fetal Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry; D024002:HMGB Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D028341:Activins; D055415:Bone Morphogenetic Protein 4; D005326:Fetal Proteins; D016222:Fibroblast Growth Factor 2; D024002:HMGB Proteins; D053605:Leukemia Inhibitory Factor; D016256:Lewis X Antigen; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C511606:Sox17 protein, mouse; C527783:Sox2 protein, mouse