Combining small molecules for cell reprogramming through an interatomic analysis.
The knowledge available about the application and generation of induced pluripotent stem cells (iPSC) has grown since their discovery, and new techniques to enhance the reprogramming process have been described. Among the new approaches to induce iPSC that have gained great attention is the use of small molecules for reprogramming. The application of small molecules, unlike genetic manipulation, provides for control of the reprogramming process through the shifting of concentrations and the combination of different molecules. However, different researchers have reported the use of "reprogramming cocktails" with variable results and drug combinations. Thus, the proper combination of small molecules for successful and enhanced reprogramming is a matter for discussion. However, testing all potential drug combinations in different cell lineages is very costly and time-consuming. Therefore, in this article, we discuss the use of already employed molecules for iPSC generation, followed by the application of systems chemo-biology tools to create different data sets of protein-protein (PPI) and chemical-protein (CPI) interaction networks based on the knowledge of already used and new reprogramming cocktail combinations. We further analyzed the biological processes associated with PPI-CPI networks and provided new potential protein targets to be inhibited or expressed for stem cell reprogramming. In addition, we applied a new interference analysis to prospective targets that could negatively affect the classical pluripotency-associated factors (SOX2, NANOG, KLF4 and OCT4) and thus potentially improve reprogramming protocols.
Centro de Biotecnologia da Universidade Federal do Rio Grande do Sul, Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500 - Prédio 43421 - Sala 219, Porto Alegre, Caixa Postal 15005, RS - Brazil. diegobonatto@gmail.com.
Bruno César
BC
Feltes
Diego
D
Bonatto
D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D065150:Cellular Reprogramming / Q000187:drug effects* / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008954:Models, Biological; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D054852:Small Molecule Libraries