Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells
Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506119302442 |
| _version_ | 1819153203949731840 |
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| author | Brit Gracy David Hideaki Fujita Kyota Yasuda Kazuko Okamoto Yulia Panina Junya Ichinose Osamu Sato Masanobu Horie Taro Ichimura Yasushi Okada Tomonobu M Watanabe |
| author_facet | Brit Gracy David Hideaki Fujita Kyota Yasuda Kazuko Okamoto Yulia Panina Junya Ichinose Osamu Sato Masanobu Horie Taro Ichimura Yasushi Okada Tomonobu M Watanabe |
| author_sort | Brit Gracy David |
| collection | DOAJ |
| description | Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We here investigated the machinery of the mechanotransduction based on the finding that spontaneous differentiation of mESCs was inhibited with the downregulation of ROCK2 in cells attached to soft substrates. On examining the effects of actin bindings to both focal adhesions and cell junctions in cells on soft substrates, co-localization of actin filaments and α-catenin, which links actin to E-cadherin, decreased after differentiation induction. Also, disrupting actin-nucleus mechanical link through dominant negative assay of Nesprins helps to sustain the pluripotency genes; thus, revealing that mechanical strain relayed by actin-Nesprin connection is required for the initiation of the differentiation process. Keywords: Embryonic stem cells, Stem cell pluripotency, Nesprin |
| first_indexed | 2024-12-22T15:01:28Z |
| format | Article |
| id | doaj.art-4b60e7cff38a48d3a67fde8918077a42 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-12-22T15:01:28Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-4b60e7cff38a48d3a67fde8918077a422022-12-21T18:22:07ZengElsevierStem Cell Research1873-50612019-12-0141Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cellsBrit Gracy David0Hideaki Fujita1Kyota Yasuda2Kazuko Okamoto3Yulia Panina4Junya Ichinose5Osamu Sato6Masanobu Horie7Taro Ichimura8Yasushi Okada9Tomonobu M Watanabe10RIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Graduate School of Frontier Bioscience, Osaka University, 1-3 Yamadaoka Suita-shi, Osaka, 565-0871, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Waseda Bioscience Research Institute in Singapore (WABIOS), 11 Biopolis Way, #05-02, Helios, 138667, SingaporeGraduate School of Integrated Sciences for Life, Hiroshima University, 1-3-2 Kagamiyama, Higashi-Hiroshima-shi, Hiroshima, 739-8511, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Graduate School of Frontier Bioscience, Osaka University, 1-3 Yamadaoka Suita-shi, Osaka, 565-0871, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, JapanDepartment of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX75708, USARadioisotope Research Center, Division of Biochemical Engineering, Kyoto University, Yoshida, Konoe-cho, Sakyo-ku, Kyoto, 606-8501, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Department of Transdimensional Life Imaging, Open and Transdisciplinary Research Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Department of Physics, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanRIKEN Center for Biosystems Dynamics Research (BDR), 6-2-3 Furuedai, Suita-shi, Osaka 565-0874, Japan; Corresponding author: Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We here investigated the machinery of the mechanotransduction based on the finding that spontaneous differentiation of mESCs was inhibited with the downregulation of ROCK2 in cells attached to soft substrates. On examining the effects of actin bindings to both focal adhesions and cell junctions in cells on soft substrates, co-localization of actin filaments and α-catenin, which links actin to E-cadherin, decreased after differentiation induction. Also, disrupting actin-nucleus mechanical link through dominant negative assay of Nesprins helps to sustain the pluripotency genes; thus, revealing that mechanical strain relayed by actin-Nesprin connection is required for the initiation of the differentiation process. Keywords: Embryonic stem cells, Stem cell pluripotency, Nesprinhttp://www.sciencedirect.com/science/article/pii/S1873506119302442 |
| spellingShingle | Brit Gracy David Hideaki Fujita Kyota Yasuda Kazuko Okamoto Yulia Panina Junya Ichinose Osamu Sato Masanobu Horie Taro Ichimura Yasushi Okada Tomonobu M Watanabe Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells Stem Cell Research |
| title | Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| title_full | Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| title_fullStr | Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| title_full_unstemmed | Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| title_short | Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| title_sort | linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S1873506119302442 |
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