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First published online March 2, 2004
doi: 10.1242/10.1242/jcs.00970

Journal of Cell Science 117, 1269-1280 (2004)
Published by The Company of Biologists 2004
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Research Article

Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin

Martin F. Pera1,*, Jessica Andrade1, Souheir Houssami1, Benjamin Reubinoff1,{ddagger}, Alan Trounson1, Edouard G. Stanley1, Dorien Ward-van Oostwaard{ddagger} and Christine Mummery2,{ddagger}

1 Monash Institute of Reproduction and Development, Monash University, 246 Clayton Road, Clayton, Victoria 3168, Australia
2 The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands

* Author for correspondence (e-mail: martin.pera{at}med.monash.edu.au)

Accepted 5 November 2003

Human embryonic stem cells differentiate spontaneously in vitro into a range of cell types, and they frequently give rise to cells with the properties of extra-embryonic endoderm. We show here that endogenous signaling by bone morphogenetic protein-2 controls the differentiation of embryonic stem cells into this lineage. Treatment of embryonic stem cell cultures with the bone morphogenetic protein antagonist noggin blocks this form of differentiation and induces the appearance of a novel cell type that can give rise to neural precursors. These findings indicate that bone morphogenetic protein-2 controls a key early commitment step in human embryonic stem cell differentiation, and show that the conservation of developmental mechanisms at the cellular level can be exploited in this system – in this case, to provide a facile route for the generation of neural precursors from pluripotent cells.

Key words: Human embryonic stem cell, Noggin, Bone morphogenetic protein, Extra-embryonic endoderm, Neural, Differentiation


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