FGF signalling inhibits neural induction in human embryonic stem cells
Open Access
- 15 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (24), 4874-4884
- https://doi.org/10.1038/emboj.2011.407
Abstract
Human embryonic stem cells (hESCs) can exit the self‐renewal programme, through the action of signalling molecules, at any given time and differentiate along the three germ layer lineages. We have systematically investigated the specific roles of three signalling pathways, TGFβ/SMAD2, BMP/SMAD1, and FGF/ERK, in promoting the transition of hESCs into the neuroectoderm lineage. In this context, inhibition of SMAD2 and ERK signalling served to cooperatively promote exit from hESC self‐renewal through the rapid downregulation of NANOG and OCT4. In contrast, inhibition of SMAD1 signalling acted to maintain SOX2 expression and prevent non‐neural differentiation via HAND1. Inhibition of FGF/ERK upregulated OTX2 that subsequently induced the neuroectodermal fate determinant PAX6, revealing a novel role for FGF2 in indirectly repressing PAX6 in hESCs. Combined inhibition of the three pathways hence resulted in highly efficient neuroectoderm formation within 4 days, and subsequently, FGF/ERK inhibition promoted rapid differentiation into peripheral neurons. Our study assigns a novel, biphasic role to FGF/ERK signalling in the neural induction of hESCs, which may also have utility for applications requiring the rapid and efficient generation of peripheral neurons.Keywords
This publication has 44 references indexed in Scilit:
- Niche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem CellPLoS Biology, 2005
- Basic Fibroblast Growth Factor Activates ERK and Induces c-Fos in Human Embryonic Stem Cell Line MizhES1Stem Cells and Development, 2005
- High‐Efficiency RNA Interference in Human Embryonic Stem CellsThe International Journal of Cell Cloning, 2005
- Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cellsNature Methods, 2005
- Mechanisms and perspectives on differentiation of autonomic neuronsDevelopmental Biology, 2005
- Regulation ofOtx2expression and its functions in mouse epiblast and anterior neuroectodermDevelopment, 2004
- Derivation of Embryonic Stem-Cell Lines from Human BlastocystsThe New England Journal of Medicine, 2004
- Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist nogginJournal of Cell Science, 2004
- Conversion of embryonic stem cells into neuroectodermal precursors in adherent monocultureNature Biotechnology, 2003
- In vitro differentiation of transplantable neural precursors from human embryonic stem cellsNature Biotechnology, 2001