Letter abstract


Nature Biotechnology 27, 275 - 280 (2009)
Published online: 1 March 2009 | Corrected online: 16 March 2009 | doi:10.1038/nbt.1529



There is a Corrigenda (May 2009) associated with this Letter.

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

Stuart M Chambers1, Christopher A Fasano1, Eirini P Papapetrou2, Mark Tomishima1,2, Michel Sadelain2,3 & Lorenz Studer1,2,4

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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.

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  1. Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave., New York, New York 10065, USA.
  2. Center for Cell Engineering, Sloan-Kettering Institute, 1275 York Ave., New York, New York 10065, USA.
  3. Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, 1275 York Ave., New York, New York 10065, USA
  4. Department of Neurosurgery, Sloan-Kettering Institute, 1275 York Ave., New York, New York 10065, USA.

Correspondence to: Lorenz Studer1,2,4 e-mail: studerl@mskcc.org

Correspondence to: Stuart M Chambers1 e-mail: chambers@mskcc.org

* In the version of this article initially published, the unit (nM) for the amount of TGF-b inhibitor (Tocris) reported in the Methods section "Neural induction" was incorrect. The correct unit is muM. The error has been corrected in the HTML and PDF versions of the article.