Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells.
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.
Xu
Ren-He
RH
WiCell Research Institute, Madison, Wisconsin 53707, USA. rxu@wicell.org
Peck
Ruthann M
RM
Li
Dong S
DS
Feng
Xuezhu
X
Ludwig
Tenneille
T
Thomson
James A
JA
D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000378:metabolism*; D002352:Carrier Proteins; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2; D000099176:Noggin Protein