Department of Ophthalmology and Visual Sciences
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Cellular and Molecular Physiology | Developmental Biology | Embryonic Structures | Enzymes and Coenzymes | Genetic Phenomena | Nucleic Acids, Nucleotides, and Nucleosides
The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq analysis and qRT-PCR showed that RIP3 KO MEFs expressed lower levels of genes that control cell cycle progression and cell division and higher levels of extracellular matrix-regulating genes. The growth rate of RIP3 KO MEFs was significantly slower than WT MEFs. These findings can partially explain the inhibitory effects of RIP3 deletion on iPSCs generation and show for the first time that the necroptosis kinase RIP3 plays an important role in iPSC reprogramming. In contrast to RIP3, the kinase and scaffolding functions of RIPK1 appeared to have distinct effects on reprogramming.
Cell death, Necroptosis, Programmed necrosis, RIP, RIPK, RIPK3, Reprogramming
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© 2019 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
DOI of Published Version
Stem Cell Res. 2019 Mar;35:101387. doi: 10.1016/j.scr.2019.101387. Epub 2019 Jan 23. Link to article on publisher's site
Stem cell research
Al-Moujahed A, Tian B, Efstathiou NE, Konstantinou EK, Hoang M, Lin H, Miller JW, Vavvas DG. (2019). Receptor interacting protein kinase 3 (RIP3) regulates iPSCs generation through modulating cell cycle progression genes. Open Access Articles. https://doi.org/10.1016/j.scr.2019.101387. Retrieved from https://escholarship.umassmed.edu/oapubs/3723
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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