論文 - 詳細
| RRC ID | 45477 |
|---|---|
| 著者 | Haque A, Adnan N, Motazedian A, Akter F, Hossain S, Kutsuzawa K, Nag K, Kobatake E, Akaike T. |
| タイトル | An Engineered N-Cadherin Substrate for Differentiation, Survival, and Selection of Pluripotent Stem Cell-Derived Neural Progenitors. |
| ジャーナル | PLoS One |
| Abstract |
For stem cell-based treatment of neurodegenerative diseases a better understanding of key developmental signaling pathways and robust techniques for producing neurons with highest homogeneity are required. In this study, we demonstrate a method using N-cadherin-based biomimetic substrate to promote the differentiation of mouse embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) without exogenous neuro-inductive signals. We showed that substrate-dependent activation of N-cadherin reduces Rho/ROCK activation and β-catenin expression, leading to the stimulation of neurite outgrowth and conversion into cells expressing neural/glial markers. Besides, plating dissociated cells on N-cadherin substrate can significantly increase the differentiation yield via suppression of dissociation-induced Rho/ROCK-mediated apoptosis. Because undifferentiated ESCs and iPSCs have low affinity to N-cadherin, plating dissociated cells on N-cadherin-coated substrate increase the homogeneity of differentiation by purging ESCs and iPSCs (~30%) from a mixture of undifferentiated cells with NPCs. Using this label-free cell selection approach we enriched differentiated NPCs plated as monolayer without ROCK inhibitor. Therefore, N-cadherin biomimetic substrate provide a powerful tool for basic study of cell-material interaction in a spatially defined and substrate-dependent manner. Collectively, our approach is efficient, robust and cost effective to produce large quantities of differentiated cells with highest homogeneity and applicable to use with other types of cells. |
| 巻・号 | 10(8) |
| ページ | e0135170 |
| 公開日 | 2015-1-1 |
| DOI | 10.1371/journal.pone.0135170 |
| PII | PONE-D-15-25411 |
| PMID | 26244942 |
| PMC | PMC4526632 |
| MeSH | Animals Blotting, Western Cadherins / genetics* Cadherins / metabolism Cell Culture Techniques / methods Cell Differentiation / genetics* Cell Line Cell Survival / genetics Embryonic Stem Cells / metabolism Gene Expression Immunoglobulin Fc Fragments / genetics Immunoglobulin Fc Fragments / metabolism Induced Pluripotent Stem Cells / metabolism Mice Microscopy, Confocal Neural Stem Cells / metabolism* Neurites / physiology Pluripotent Stem Cells / metabolism* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Reproducibility of Results Reverse Transcriptase Polymerase Chain Reaction Time-Lapse Imaging beta Catenin / metabolism rho GTP-Binding Proteins / metabolism rho-Associated Kinases / metabolism |
| IF | 2.74 |
| 引用数 | 10 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |