Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming
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Authors
Sakurai, KumiTalukdar, Indrani
Patil, Veena S.
Dang, Jason
Li, Zhonghan
Chang, Kung-Yen
Lu, Chih-Chung
Delorme-Walker, Violaine
Dermardirossian, Celine
Anderson, Karen
Hanein, Dorit
Yang, Chao-Shun
Wu, Dongmei
Liu, Yang
Rana, Tariq M.
Student Authors
Chao-Shun YangUMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2014-04-03Keywords
Actin Depolymerizing Factors; Animals; *Cell Differentiation; Cells, Cultured; Cellular Reprogramming; Cytoskeleton; Embryo, Mammalian; Embryonic Stem Cells; Fibroblasts; Gene Regulatory Networks; Humans; Induced Pluripotent Stem Cells; Lim Kinases; Mice; Microscopy, Confocal; Phosphorylation; Protein-Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering; TeratomaCell and Developmental Biology
Cell Biology
Genetics and Genomics
Genomics
Metadata
Show full item recordAbstract
The creation of induced pluripotent stem cells (iPSCs) from somatic cells by ectopic expression of transcription factors has galvanized the fields of regenerative medicine and developmental biology. Here, we report a kinome-wide RNAi-based analysis to identify kinases that regulate somatic cell reprogramming to iPSCs. We prepared 3,686 small hairpin RNA (shRNA) lentiviruses targeting 734 kinase genes covering the entire mouse kinome and individually examined their effects on iPSC generation. We identified 59 kinases as barriers to iPSC generation and characterized seven of them further. We found that shRNA-mediated knockdown of the serine/threonine kinases TESK1 or LIMK2 promoted mesenchymal-to-epithelial transition, decreased COFILIN phosphorylation, and disrupted Actin filament structures during reprogramming of mouse embryonic fibroblasts. Similarly, knockdown of TESK1 in human fibroblasts also promoted reprogramming to iPSCs. Our study reveals the breadth of kinase networks regulating pluripotency and identifies a role for cytoskeletal remodeling in modulating the somatic cell reprogramming process.Source
Cell Stem Cell. 2014 Apr 3;14(4):523-34. doi: 10.1016/j.stem.2014.03.001. Link to article on publisher's siteDOI
10.1016/j.stem.2014.03.001Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33402PubMed ID
24702998Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.stem.2014.03.001