Abstract
Human embryonic stem cells differentiate spontaneously in vitro into a range of cell types, and they frequently give rise to cells with the properties of extra-embryonic endoderm. We show here that endogenous signaling by bone morphogenetic protein-2 controls the differentiation of embryonic stem cells into this lineage. Treatment of embryonic stem cell cultures with the bone morphogenetic protein antagonist noggin blocks this form of differentiation and induces the appearance of a novel cell type that can give rise to neural precursors. These findings indicate that bone morphogenetic protein-2 controls a key early commitment step in human embryonic stem cell differentiation, and show that the conservation of developmental mechanisms at the cellular level can be exploited in this system--in this case, to provide a facile route for the generation of neural precursors from pluripotent cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein Receptors, Type II
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Bone Morphogenetic Proteins / antagonists & inhibitors*
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / pharmacology*
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Bone Morphogenetic Proteins / physiology*
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Carrier Proteins
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cells, Cultured
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DNA Primers / genetics
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Humans
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Stem Cells / cytology*
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Stem Cells / drug effects*
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Stem Cells / physiology
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Transforming Growth Factor beta*
Substances
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BMP2 protein, human
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Carrier Proteins
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DNA Primers
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RNA, Messenger
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Recombinant Proteins
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Transforming Growth Factor beta
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recombinant human bone morphogenetic protein-2
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noggin protein
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Protein Serine-Threonine Kinases
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BMPR2 protein, human
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Bone Morphogenetic Protein Receptors, Type II