scholarly journals Effects of Culture Conditions and Bone Morphogenetic Protein 2 on Extent of Chondrogenesis from Human Embryonic Stem Cells

Stem Cells ◽  
2007 ◽  
Vol 25 (4) ◽  
pp. 950-960 ◽  
Author(s):  
Wei Seong Toh ◽  
Zheng Yang ◽  
Hua Liu ◽  
Boon Chin Heng ◽  
Eng Hin Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Bone Morphogenetic Protein ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals Rapamycin efficiently promotes cardiac differentiation of mouse embryonic stem cells

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Qin Lu ◽  
Yinan Liu ◽  
Yang Wang ◽  
Weiping Wang ◽  
Zhe Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Early Stage ◽  
Mammalian Target Of Rapamycin ◽  
Embryonic Stem ◽  
Cardiac Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Cardiac Transcription Factors ◽  
20 Nm

To investigate the effects of rapamycin on cardiac differentiation, murine embryonic stem cells (ESCs) were induced into cardiomyocytes by 10−4 M ascorbic acid (AA), 20 nM rapamycin alone or 0.01% solvent DMSO. We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then, the ESCs were treated with AA and rapamycin (20 nM) or AA and DMSO (0.01%) as a control. Compared with control, mouse ESCs (mESCs) treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by the percentage of beating embryonic bodies (EBs), the immunofluorescence and FACS analysis. Rapamycin significantly increased the expression of a panel of cardiac markers including Gata4, α-Mhc, β-Mhc, and Tnnt2. Additionally, rapamycin enhanced the expression of mesodermal and cardiac transcription factors such as Mesp1, Brachyury T, Eomes, Isl1, Gata4, Nkx2.5, Tbx5, and Mef2c. Mechanistic studies showed that rapamycin inhibits Wnt/β-catenin and Notch signaling but promotes the expression of fibroblast growth factor (Fgf8), Fgf10, and Nodal at early stage, and bone morphogenetic protein 2 (Bmp 2) at later stages. Sequential treatment of rapamycin showed that rapamycin promotes cardiac differentiation at the early and later stages. Interestingly, another mammalian target of rapamycin (mTOR) inhibitor Ku0063794 (1 µM) had similar effects on cardiomyogenesis. In conclusion, our results highlight a practical approach to generate cardiomyocytes from mESCs by rapamycin.

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