Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling

Current neural induction protocols for human embryonic stem (hES) cells rely on embryoid body formation, stromal feeder co-culture or selective survival conditions. Each strategy has considerable drawbacks, such as poorly defined culture conditions, protracted differentiation and low yield. Here we...

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Bibliographic Details
Published in:Nature biotechnology 2009-03, Vol.27 (3), p.275-280
Main Authors: Chambers, Stuart M, Studer, Lorenz, Fasano, Christopher A, Papapetrou, Eirini P, Tomishima, Mark, Sadelain, Michel
Format: Article
Language:English
Subjects:
Agriculture
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Carrier Proteins - pharmacology
Cell culture
Cell Culture Techniques
Cell Differentiation
Cellular signal transduction
Central nervous system
Control
Embryonic stem cells
Embryonic Stem Cells - cytology
Fundamental and applied biological sciences. Psychology
Genetic aspects
Health. Pharmaceutical industry
Humans
Industrial applications and implications. Economical aspects
letter
Life Sciences
Mesencephalon - cytology
Miscellaneous
Neurology
Neurons - cytology
Physiological aspects
Pluripotent Stem Cells - cytology
Signal transduction
Signal Transduction - drug effects
Smad Proteins - drug effects
Smad Proteins - metabolism
Stem cells
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Summary:Current neural induction protocols for human embryonic stem (hES) cells rely on embryoid body formation, stromal feeder co-culture or selective survival conditions. Each strategy has considerable drawbacks, such as poorly defined culture conditions, protracted differentiation and low yield. Here we report that the synergistic action of two inhibitors of SMAD signaling, Noggin and SB431542, is sufficient to induce rapid and complete neural conversion of >80% of hES cells under adherent culture conditions. Temporal fate analysis reveals the appearance of a transient FGF5+ epiblast-like stage followed by PAX6+ neural cells competent to form rosettes. Initial cell density determines the ratio of central nervous system and neural crest progeny. Directed differentiation of human induced pluripotent stem (hiPS) cells into midbrain dopamine and spinal motoneurons confirms the robustness and general applicability of the induction protocol. Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt.1529