Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentia...Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 （CT-1） on cardiomyocyte differentiation from mouse induced pluripotent stem cells （miPSCs） and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration （10 ng/mL） and duration （from day 3 to day 14） of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of a-myosin heavy chain （ct-MHC） and cardiac troponin I （cTn I） positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT- 1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT- 1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1 signaling pathway.展开更多
Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanak...Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,展开更多
基金This work was supported by the National Funds for Distinguished Young Scientists of China （No. 81325009） and National Nature Science Foundation of China （No. 81270168, No. 81227901）, （Feng Cao BWS12J037）, Innovation Team granted by Ministry of Education PRC （IRT1053）, National Basic Research Program of China （2012CB518101）. Shaanxi Province Program （2013K12-02-03, 2014KCT-20）. The authors declare no conflict of interest.
文摘Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 （CT-1） on cardiomyocyte differentiation from mouse induced pluripotent stem cells （miPSCs） and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration （10 ng/mL） and duration （from day 3 to day 14） of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of a-myosin heavy chain （ct-MHC） and cardiac troponin I （cTn I） positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT- 1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT- 1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1 signaling pathway.
基金supported by the grants from the "Strategic Priority Research Program" of the Chinese Academy of Sciences (No. XDA01020100 to Q.Z.)the China National Basic Research Program (No. 2012CBA01300 to Q.Z.)the National Science Foundation of China (No. 91319308 to Q.Z.,31201105 to L.L. and 31371516 to W.L.)
文摘Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,
