PMID- 22213113 OWN - NLM STAT- MEDLINE DCOM- 20120717 LR - 20230207 IS - 1549-4918 (Electronic) IS - 1066-5099 (Print) IS - 1066-5099 (Linking) VI - 30 IP - 4 DP - 2012 Apr TI - Thermal stability of fibroblast growth factor protein is a determinant factor in regulating self-renewal, differentiation, and reprogramming in human pluripotent stem cells. PG - 623-30 LID - 10.1002/stem.1021 [doi] AB - 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. CI - Copyright (c) 2011 AlphaMed Press. FAU - Chen, Guokai AU - Chen G AD - Morgridge Institute for Research, Madison, Wisconsin, USA. FAU - Gulbranson, Daniel R AU - Gulbranson DR FAU - Yu, Pengzhi AU - Yu P FAU - Hou, Zhonggang AU - Hou Z FAU - Thomson, James A AU - Thomson JA LA - eng GR - U01 ES017166/ES/NIEHS NIH HHS/United States GR - U01ES017166/ES/NIEHS NIH HHS/United States GR - RR-05-19/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (Mutant Proteins) RN - 0 (Receptors, Fibroblast Growth Factor) RN - 62031-54-3 (Fibroblast Growth Factors) RN - 9005-49-6 (Heparin) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Cell Differentiation/*drug effects MH - Cell Proliferation/drug effects MH - Cellular Reprogramming/*drug effects MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fibroblast Growth Factors/metabolism/*pharmacology MH - Heparin/metabolism MH - Humans MH - Mutant Proteins/metabolism MH - Mutation/genetics MH - Phosphorylation/drug effects MH - Pluripotent Stem Cells/*cytology/*drug effects/enzymology MH - Protein Stability/drug effects MH - Receptors, Fibroblast Growth Factor/metabolism MH - *Temperature PMC - PMC3538808 MID - NIHMS428275 COIS- Disclosure of Potential Conflicts of Interest J.A.T. is a founder, stockowner, consultant, and board member of Cellular Dynamics International (CDI). He also serves as scientific advisor to and has financial interests in Tactics II Stem Cell Ventures. EDAT- 2012/01/04 06:00 MHDA- 2012/07/18 06:00 PMCR- 2013/01/08 CRDT- 2012/01/04 06:00 PHST- 2012/01/04 06:00 [entrez] PHST- 2012/01/04 06:00 [pubmed] PHST- 2012/07/18 06:00 [medline] PHST- 2013/01/08 00:00 [pmc-release] AID - 10.1002/stem.1021 [doi] PST - ppublish SO - Stem Cells. 2012 Apr;30(4):623-30. doi: 10.1002/stem.1021.