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A critical role for p38MAPK signalling pathway during reprogramming of human fibroblasts to iPSCs

Lookup NU author(s): Dr Irina Neganova, Dr Valeria Chichagova, Professor Lyle Armstrong, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) holds enormous promise for regenerative medicine. Reprogramming is a stepwise process with well-defined stages of initiation, maturation and stabilisation which are critically dependent on interactions between key pluripotency transcription factors, epigenetic regulators and signalling pathways. In this manuscript we have investigated the role of p38 MAPK signalling pathway and have shown a subpopulation- and phase-specific pattern of activation occurring during the initiation and maturation stage of reprogramming in partially and fully reprogrammed cells respectively. Downregulation of p38 MAPK activity via RNA interference or small molecule inhibitor led to cell accumulation in G1 phase of the cell cycle and reduced expression of cell cycle regulators during the initiation stage of reprogramming. This was associated with a significant downregulation of key pluripotency marker expression, disruption of mesenchymal to epithelial transition (MET), increased expression of differentiation markers and presence of partially reprogrammed cells which retained a typical gene expression profile of mesendodermal cells and were unable to progress to fully reprogrammed phenotype. Together our data indicate an important role for p38 MAPK activity in proliferation, MET progression and establishment of pluripotent phenotype, which are necessary steps for the development of human iPSCs.


Publication metadata

Author(s): Neganova I, Chichagova V, Armstrong L, Lako M

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2017

Volume: 7

Online publication date: 03/02/2017

Acceptance date: 09/12/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/srep41693

DOI: 10.1038/srep41693


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