Kinome-wide Functional Analysis Highlights the Role of Cytoskeletal Remodeling in Somatic Cell Reprogramming

详细信息    查看全文

• 作者：Kumi Sakurai¹ ; ⁹ ; Indrani Talukdar¹ ; ⁹ ; Veena S. Patil¹ ; ⁹ ; Jason Dang¹ ; ² ; Zhonghan Li¹ ; ³ ; Kung-Yen Chang¹ ; Chih-Chung Lu¹ ; Violaine Delorme-Walker⁴ ; Celine DerMardirossian⁴ ; Karen Anderson⁵ ; Dorit Hanein⁵ ; Chao-Shun Yang¹ ; ³ ; Dongmei Wu⁶ ; Yang Liu⁶ ; Tariq M. Rana¹ ; ³ ; ⁷ ; ⁸ ; ^{trana@sanfordburnham.org" class="auth_mail}
• 刊名：Cell Stem Cell
• 出版年：3 April, 2014
• 年：2014
• 卷：14
• 期：4
• 页码：523-534
• 全文大小：4003 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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.