Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin.
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.
Monash Institute of Reproduction and Development, Monash University, 246 Clayton Road, Clayton, Victoria 3168, Australia. martin.pera@med.monash.edu.au
Martin F
MF
Pera
Jessica
J
Andrade
Souheir
S
Houssami
Benjamin
B
Reubinoff
Alan
A
Trounson
Edouard G
EG
Stanley
Dorien
D
Ward-van Oostwaard
Christine
C
Mummery
D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525718:BMP2 protein, human; C499469:recombinant human bone morphogenetic protein-2; C498218:BMPR2 protein, human