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Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming. | LitMetric

Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming.

Cell Stem Cell

Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Pediatrics, Rady Children's Hospital San Diego and University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA. Electronic address:

Published: April 2014

AI Article Synopsis

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071169PMC
http://dx.doi.org/10.1016/j.stem.2014.03.001DOI Listing

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