Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming
Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
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; Teratoma
Cell and Developmental Biology | Cell Biology | Genetics and Genomics | Genomics
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.
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Citation: Cell Stem Cell. 2014 Apr 3;14(4):523-34. doi: 10.1016/j.stem.2014.03.001. Link to article on publisher's site
DOI of Published Version
Cell stem cell
Sakurai, Kumi; Talukdar, 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; and Rana, Tariq M., "Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming" (2014). GSBS Student Publications. 1927.