Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling Journal Article
| Authors: | Chambers, S. M.; Fasano, C. A.; Papapetrou, E. P.; Tomishima, M.; Sadelain, M.; Studer, L. |
| Article Title: | Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling |
| Abstract: | 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<sup>+</sup> epiblast-like stage followed by PAX6<sup>+</sup> 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. © 2009 Nature America, Inc. All rights reserved. |
| Keywords: | signal transduction; human cell; signaling; smad protein; embryo; embryonic stem cell; clinical protocol; neural stem cell; cell differentiation; neurons; cell assay; feeding; central nervous system; disease model; cell culture; carrier proteins; progeny; cell culture techniques; smad proteins; embryonic stem cells; cell densities; central nervous systems; co cultures; culture conditions; embryoid bodies; human embryonic stem (hes) cell; low yields; midbrain; neural cells; neural crests; pluripotent; regenerative medicines; smad signaling; synergistic actions; 4 [4 (1,3 benzodioxol 5 yl) 5 (2 pyridinyl) 1h imidazol 2 yl]benzamide; fibroblast growth factor 5; noggin; transcription factor pax6; cell density; cell regeneration; fetus; gene induction; mesencephalon; neural crest; pluripotent stem cell; rosette formation; spinal cord motoneuron; pluripotent stem cells; ips |
| Journal Title: | Nature Biotechnology |
| Volume: | 27 |
| Issue: | 3 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-03-01 |
| Start Page: | 275 |
| End Page: | 280 |
| Language: | English |
| DOI: | 10.1038/nbt.1529 |
| PUBMED: | 19252484 |
| PROVIDER: | scopus |
| PMCID: | PMC2756723 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 62" - "Export Date: 30 November 2010" - "CODEN: NABIF" - "Source: Scopus" |
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