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Lookup NU author(s): Dr iRINA Neganova, Lewis Cotts, Dr Andrew Banks, Katja Gassner, Professor Lyle Armstrong, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Direct reprogramming of human somatic cells towards induced pluripotent stem cells holds great promise for regenerative medicine and basic biology. We used a high-throughput siRNA screening assay in the initiation phase of reprogramming for 784 genes belonging to kinase and phosphatase families and identified 68 repressors and 22 effectors. Six new candidates belonging to the family of the G protein–coupled receptors (GPCRs) were identified suggesting an important role for this key signalling pathway during somatic cell induced reprogramming. Downregulation of one of the key GPCR effectors, EDG5 impacted the maintenance of pluripotency, actin cytoskeleton organisation, colony integrity and focal adhesions in hESCs which were associated with the alteration in the RhoA-Rock-Cofilin-Paxillin-actin signalling pathway. Similarly, downregulation of EDG5 during the initiation stage of somatic cell induced reprogramming resulted in alteration of cytoskeleton, loss of human iPSC colony integrity and a significant reduction in partially and fully reprogrammed cells as well as the number of alkaline phosphatase positive colonies at the end of the reprogramming process. Together these data point to an important role for EDG5 in maintenance and acquisition of pluripotency.
Author(s): Neganova I, Cotts L, Banks P, Gassner K, Armstrong L, Ladds G, Lako M
Publication type: Article
Publication status: Published
Journal: Stem Cells
Year: 2018
Volume: 37
Issue: 3
Pages: 318-331
Print publication date: 01/03/2019
Online publication date: 04/12/2018
Acceptance date: 29/10/2018
Date deposited: 04/11/2018
ISSN (print): 1066-5099
ISSN (electronic): 1549-4918
Publisher: AlphaMed Press, Inc.
URL: https://doi.org/10.1002/stem.2954
DOI: 10.1002/stem.2954
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