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dc.contributor.authorSakurai, Kumi
dc.contributor.authorTalukdar, Indrani
dc.contributor.authorPatil, Veena S.
dc.contributor.authorDang, Jason
dc.contributor.authorLi, Zhonghan
dc.contributor.authorChang, Kung-Yen
dc.contributor.authorLu, Chih-Chung
dc.contributor.authorDelorme-Walker, Violaine
dc.contributor.authorDermardirossian, Celine
dc.contributor.authorAnderson, Karen
dc.contributor.authorHanein, Dorit
dc.contributor.authorYang, Chao-Shun
dc.contributor.authorWu, Dongmei
dc.contributor.authorLiu, Yang
dc.contributor.authorRana, Tariq M.
dc.date2022-08-11T08:08:56.000
dc.date.accessioned2022-08-23T16:12:28Z
dc.date.available2022-08-23T16:12:28Z
dc.date.issued2014-04-03
dc.date.submitted2015-09-21
dc.identifier.citationCell Stem Cell. 2014 Apr 3;14(4):523-34. doi: 10.1016/j.stem.2014.03.001. <a href="http://dx.doi.org/10.1016/j.stem.2014.03.001">Link to article on publisher's site</a>
dc.identifier.issn1875-9777 (Electronic)
dc.identifier.doi10.1016/j.stem.2014.03.001
dc.identifier.pmid24702998
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33402
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24702998&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071169/
dc.subjectActin 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
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectGenetics and Genomics
dc.subjectGenomics
dc.titleKinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming
dc.typeJournal Article
dc.source.journaltitleCell stem cell
dc.source.volume14
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1927
dc.identifier.contextkey7622779
html.description.abstract<p>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.</p>
dc.identifier.submissionpathgsbs_sp/1927
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages523-34
dc.contributor.studentChao-Shun Yang


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