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First published online July 7, 2005
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Submitted on March 14, 2005
Accepted on June 21, 2005

Experimental Protocols for Embryonic Stem Cell Research

Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking BMP signaling

Lesley Gerrard 1, Leigh Rodgers 1, Wei Cui 1*

1 Department of Gene Function & Development, Roslin Institute, Roslin, Midlothian, EH25 9PS, UK.

* To whom correspondence should be addressed. E-mail: wei.cui{at}bbsrc.ac.uk.


  Abstract

Human embryonic stem cells (hESCs) have extensive self-renewal capacity and are competent to differentiate into any cell types 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. Here 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 BMP 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 finding will provide a platform for studying the molecular mechanism controlling neural differentiation.

Key Words. human embryonic stem cell, neural differentiation, noggin, BMP, Oct4




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