Open AccessThermal Stability of Fibroblast Growth Factor Protein Is a Determinant Factor in Regulating Self‐Renewal, Differentiation, and Reprogramming in Human Pluripotent Stem Cells
Author(s) -
Chen Guokai,
Gulbranson Daniel R.,
Yu Pengzhi,
Hou Zhonggang,
Thomson James A.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1021
Subject(s) - biology , homeobox protein nanog , microbiology and biotechnology , fgf1 , fibroblast growth factor , induced pluripotent stem cell , reprogramming , fibroblast growth factor receptor , fibroblast growth factor receptor 3 , embryonic stem cell , stem cell , fibroblast growth factor receptor 2 , fibroblast growth factor receptor 4 , growth factor , receptor , genetics , cell , gene
Abstract Fibroblast growth factor (FGF), transforming growth factor (TGF)/Nodal, and Insulin/insulin‐like growth factor (IGF) signaling pathways are sufficient to maintain human embryonic stem cells (ESCs) and induced pluripotent stem cells in a proliferative, undifferentiated state. Here, we show that only a few FGF family members (FGF2, FGF4, FGF6, and FGF9) are able to sustain strong extracellular‐signal‐regulated kinase (ERK) phosphorylation and NANOG expression levels in human ESCs. Surprisingly, FGF1, which is reported to target the same set of receptors as FGF2, fails to sustain ERK phosphorylation and NANOG expression under standard culture conditions. We find that the failure of FGF1 to sustain ES is due to thermal instability of the wild‐type protein, not receptor specificity, and that a mutated thermal‐stable FGF1 sustains human ESCs and supports both differentiation and reprogramming protocols. S TEM C ELLS 2012; 30:623–630