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| Home > Articles > Published articles > Global proteomic and methylome analysis in human induced pluripotent stem cells reveals overexpression of a human TLR3 affecting proper innate immune response signaling |
(Universitat de Barcelona. Departament de Biomedicina) (Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigació Biomèdica de Bellvitge) (Hospital Clínic i Provincial de Barcelona) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Universitat de Barcelona. Departament de Biomedicina) (Universitat de Barcelona. Departament de Biomedicina)
| Date: | 2019 |
| Abstract: | When considering the clinical applications of autologous cell replacement therapy of human induced pluripotent stem cells (iPSC)-derived cells, there is a clear need to better understand what the immune response will be before we embark on extensive clinical trials to treat or model human disease. We performed a detailed assessment comparing human fibroblast cell lines (termed F1) reprogrammed into human iPSC and subsequently differentiated back to fibroblast cells (termed F2) or other human iPSC-derived cells including neural stem cells (NSC) made from either retroviral, episomal, or synthetic mRNA cell reprogramming methods. Global proteomic analysis reveals the main differences in signal transduction and immune cell protein expression between F1 and F2 cells, implicating wild type (WT) toll like receptor protein 3 (TLR3). Furthermore, global methylome analysis identified an isoform of the human TLR3 gene that is not epigenetically reset correctly upon differentiation to F2 cells resulting in a hypomethylated transcription start site in the TLR3 isoform promoter and overexpression in most human iPSC-derived cells not seen in normal human tissue. The human TLR3 isoform in human iPSC-NSC functions to suppress NF-KB p65 signaling pathway in response to virus (Poly IC), suggesting suppressed immunity of iPSC-derived cells to viral infection. The sustained WT TLR3 and TLR3 isoform overexpression is central to understanding the altered immunogenicity of human iPSC-derived cells calling for screening of human iPSC-derived cells for TLR3 expression levels before applications. Stem Cells 2019;37:476-488. |
| Grants: | European Commission 311736 European Commission 305421 Ministerio de Economía y Competitividad BFU2016-80870-P Ministerio de Economía y Competitividad BFU2014-54467-P Ministerio de Economía y Competitividad BFU2011-26596 Ministerio de Economía y Competitividad RYC-2010-0651 Ministerio de Economía y Competitividad FIS/P113/00699 Instituto de Salud Carlos III RD16/0011/0024 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-899 |
| Note: | Altres ajuts: the E-Rare (ERA-Net for research programs on rare diseases) and EuroRETT (a European network on Rett syndrome, funded by the European Commission under its 6th Framework Program since 2006) |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Cytokine ; Human leukocyte antigen ; Immune response ; Induced pluripotent stem cells ; Inflammation ; MHC-I ; Neural stem cells ; Toll like receptor |
| Published in: | Stem Cells, Vol. 37, issue 4 (April 2019) , p. 476-488, ISSN 1549-4918 |
