title: Early cell fate decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signalling pathways.
abstract: Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broad variety of cell types. Therefore, defining the signalling pathways that control early cell fate decisions of pluripotent stem cells represents a major task. Moreover, modelling the early steps of embryonic development in vitro may provide the best approach to produce cell types with native properties. Here, we analysed the function of key developmental growth factors such as Activin, FGF and BMP in the control of early cell fate decisions of human pluripotent stem cells. This analysis resulted in the development and validation of chemically defined culture conditions for achieving specification of human embryonic stem cells into neuroectoderm, mesendoderm and into extra-embryonic tissues. Importantly, these defined culture conditions are devoid of factors that could obscure analysis of developmental mechanisms or render the resulting tissues incompatible with future clinical applications. Importantly, the growth factor roles defined using these culture conditions similarly drove differentiation of mouse epiblast stem cells derived from post implantation embryos, thereby reinforcing the hypothesis that epiblast stem cells share a common embryonic identity with human pluripotent stem cells. Therefore the defined growth factor conditions described here represent an essential step toward the production of mature cell types from pluripotent stem cells in conditions fully compatible with clinical use ant also provide a general approach for modelling the early steps of mammalian embryonic development.
authors: Department of Surgery and Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, UK. lv225@cam.ac.uk
authors: Ludovic
authors: L
authors: Vallier
authors: Thomas
authors: T
authors: Touboul
authors: Zhenzhi
authors: Z
authors: Chng
authors: Minodora
authors: M
authors: Brimpari
authors: Nicholas
authors: N
authors: Hannan
authors: Enrique
authors: E
authors: Millan
authors: Lucy E
authors: LE
authors: Smithers
authors: Matthew
authors: M
authors: Trotter
authors: Peter
authors: P
authors: Rugg-Gunn
authors: Anne
authors: A
authors: Weber
authors: Roger A
authors: RA
authors: Pedersen
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D004475:Ectoderm / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D004707:Endoderm / Q000378:metabolism; D005855:Germ Layers / Q000166:cytology*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4