Activation of proHGF by St14 induces mouse embryonic stem cell differentiation
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Dear Editor,Embryonic stem cells (ESCs) are capable of unlimited selfrenewal and differentiation,thus generating remarkable interest in their potential therapeutic use in cell-based tissue engineering and regeneration.Stem cell based therapy has been considered as the most promising therapeutic strategy for a range of debilitating diseases (Reynolds and Lamba,2014).One key requirement for stem cell differentiation and migration is to overcome existing matrix obstacles,that endowed by multiple mechanisms including tight junctions,as well as physical properties such as the matrix geometry,nanotopography,and stiffness,etc.(Guilak et al.,2009).It was reported that adherent cells showed tensile stress in the cytoskeleton by exerting contractile forces which in tum strengthen the stiffness of the matrix (Ingber,2004).The strategy cells usually employ to disrupt the matrix obstacle is zymogen cascades mechanism that usually involved at least two proteolytic reactions that can explosively amplify the influence of extracellular signals.During this process,proteolytic activities of serine proteases,one of the most ubiquitous membrane proteases of the protease superfamily,play crucial roles by cleaving the extracellular matrix and enabling the stem cells to translocate to distant target sites (Paule et al.,2015).Facilitating the activation of extracellular signals is essential for the extracellular signaling transduction and fate decision of mESCs,as most growth factors and cytokines are usually synthesized as latent forms that require activation by the proteasesystem located on the membrane of stem cells.
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This study was supported by grants from the National Basic Research Program 973 Program Nos.2014CB964700 and 2014CB964701,the National Science Fund for Distinguished Young Scholars 81125003,the Research and Innovation Project of Shanghai Municipal Education Commission 14JC1405700 and 15ZZ059,Science and Technology Committee of Shanghai Municipality 12XD1406500,Shanghai Leading Academic Discipline Project S3201,Shu Guang Project of Shanghai Education Commission No.10GG10.