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

Stuart M Chambers1, Christopher A Fasano, Eirini P Papapetrou

  • 1Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave., New York, New York 10065, USA. chambers@mskcc.org

Nature Biotechnology
|March 3, 2009
PubMed

Insights

This study introduces a new method for neural induction using Noggin and SB431542, achieving rapid and efficient neural conversion of human stem cells. This approach simplifies protocols and enhances potential applications in regenerative medicine and disease modeling.

Area of Science:

  • Stem cell biology
  • Neuroscience
  • Developmental biology

Background:

  • Current human embryonic stem cell (hES) neural induction methods involve embryoid bodies, feeder cells, or selective survival, presenting challenges like undefined conditions, slow differentiation, and low yields.
  • These limitations hinder the effective use of hES cells in research and clinical applications.

Purpose of the Study:

  • To develop a more efficient and robust protocol for neural induction of human pluripotent stem cells.
  • To investigate the synergistic effects of Noggin and SB431542 on neural differentiation.

Main Methods:

  • Utilized a combination of Noggin and SB431542 inhibitors targeting SMAD signaling.
  • Employed adherent culture conditions for neural conversion of hES cells.
  • Analyzed temporal cell fate and directed differentiation of human induced pluripotent stem (hiPS) cells.

Main Results:

  • Achieved rapid and complete neural conversion of over 80% of hES cells using Noggin and SB431542.
  • Identified a transient epiblast-like stage (FGF5+) followed by PAX6+ neural cells.
  • Demonstrated successful directed differentiation into midbrain dopamine and spinal motoneurons from hiPS cells.

Conclusions:

  • The Noggin/SB431542 protocol offers a simplified, efficient, and robust method for neural induction of human pluripotent stem cells.
  • This protocol overcomes drawbacks of existing methods, paving the way for enhanced applications in regenerative medicine and disease modeling.
  • The method is applicable to both hES and hiPS cells, highlighting its generalizability.

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