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
PubMed ID
30703581
Repository Citation
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
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Cell Biology Commons, Cells Commons, Cellular and Molecular Physiology Commons, Developmental Biology Commons, Embryonic Structures Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons