Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling.
Human embryonic stem cells (hESCs) have extensive self-renewal capacity and are competent to differentiate into any cell type of the body. They are valuable not only for the study of early human development but also for regenerative medicine. However, how to direct differentiation of hESCs along a particular lineage pathway to a specific cell type remains a challenge. Although hESCs have been shown to differentiate in vitro into neural progenitors, the factors controlling their differentiation are poorly understood. In this study, we report the development of an in vitro adherent culture system to efficiently generate neural progenitors in which neither multicellular aggregates nor stromal cells are required. We show that inhibition of bone morphogenetic protein signaling by its antagonist noggin is sufficient to block extraembryonic cell fate, transiently sustain Oct4 gene expression, and result in robust production of neural progenitors. Our findings will provide a platform for studying the molecular mechanism controlling neural differentiation.
Department of Gene Function and Development, Roslin Institute, Roslin, Midlothian, EH25 9PS, UK.
Lesley
L
Gerrard
Leigh
L
Rodgers
Wei
W
Cui
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000494:pharmacology; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000166:cytology; D004707:Endoderm / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D050814:Octamer Transcription Factor-3; D011994:Recombinant Proteins; D000099176:Noggin Protein