UMMS Affiliation

Department of Ophthalmology and Visual Sciences

Publication Date

2019-3

Document Type

Article

Disciplines

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

Abstract

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.

Keywords

Cell death, Necroptosis, Programmed necrosis, RIP, RIPK, RIPK3, Reprogramming

Rights and Permissions

© 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

10.1016/j.scr.2019.101387

Source

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

Journal/Book/Conference Title

Stem cell research

Related Resources

Link to Article in PubMed

PubMed ID

30703581

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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