Nature Methods2, 185 - 190 (2005)
Published online: 17 February 2005; | doi:10.1038/nmeth744
Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells
Ren-He Xu1, 2, Ruthann M Peck1, Dong S Li1, Xuezhu Feng2, Tenneille Ludwig2
& James A Thomson1, 2
1
WiCell Research Institute, Madison, Wisconsin 53707, USA.
2
Department of Anatomy, University of Wisconsin-Madison Medical School, the Wisconsin National Primate Research Center and The Genome Center of Wisconsin, Madison, Wisconsin 53706, USA.
Human embryonic stem cells (hESCs) are routinely cultured on fibroblast feeder layers or in fibroblast-conditioned medium (CM). Bone morphogenetic proteins (BMPs) have previously been shown to induce hESC differentiation, in apparent contrast to mouse embryonic stem (ES) cells, in which BMP4 synergizes with leukemia inhibitory factor (LIF) to maintain self-renewal. Here we demonstrate that hESCs cultured in unconditioned medium (UM) are subjected to high levels of BMP signaling activity, which is reduced in CM. The BMP antagonist noggin synergizes with basic fibroblast growth factor (bFGF) to repress BMP signaling and sustain undifferentiated proliferation of hESCs in the absence of fibroblasts or CM. These findings suggest a basic difference in the self-renewal mechanism between mouse and human ES cells and simplify the culture of hESCs.
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