Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells
Leveraging the extraordinary potential of human pluripotent stem cells (hPSCs)requires an understanding of the mechanisms underlying cell-fate decisions. Substrate elasticity can induce differentiation by signaling through the transcriptional coactivator Yes-associated protein (YAP). Cells cultured...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125504 |
| _version_ | 1811078276410507264 |
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| author | Zaltsman, Yefim Masuko, Sayaka Bensen, Joshua J. Kiessling, Laura L |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Zaltsman, Yefim Masuko, Sayaka Bensen, Joshua J. Kiessling, Laura L |
| author_sort | Zaltsman, Yefim |
| collection | MIT |
| description | Leveraging the extraordinary potential of human pluripotent stem cells (hPSCs)requires an understanding of the mechanisms underlying cell-fate decisions. Substrate elasticity can induce differentiation by signaling through the transcriptional coactivator Yes-associated protein (YAP). Cells cultured on surfaces mimicking brain elasticity exclude YAP from their nuclei and differentiate to neurons. How YAP localization is controlled during neural differentiation has been unclear. We employed CRISPR/Cas9 to tag endogenous YAP in hPSCs and used this fusion protein to identify YAP's interaction partners. This engineered cell line revealed that neural differentiation promotes a change in YAP interactors, including a dramatic increase in angiomotin (AMOT)interaction with YAP. AMOT regulates YAP localization during differentiation. AMOT expression increases during neural differentiation and leads to YAP nuclear exclusion. Our findings that AMOT-dependent regulation of YAP helps direct hPSC fate provide insight into the molecular mechanisms by which the microenvironment can induce neural differentiation. |
| first_indexed | 2024-09-23T10:57:06Z |
| format | Article |
| id | mit-1721.1/125504 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:57:06Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1255042022-09-27T16:09:22Z Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells Zaltsman, Yefim Masuko, Sayaka Bensen, Joshua J. Kiessling, Laura L Massachusetts Institute of Technology. Department of Chemistry Leveraging the extraordinary potential of human pluripotent stem cells (hPSCs)requires an understanding of the mechanisms underlying cell-fate decisions. Substrate elasticity can induce differentiation by signaling through the transcriptional coactivator Yes-associated protein (YAP). Cells cultured on surfaces mimicking brain elasticity exclude YAP from their nuclei and differentiate to neurons. How YAP localization is controlled during neural differentiation has been unclear. We employed CRISPR/Cas9 to tag endogenous YAP in hPSCs and used this fusion protein to identify YAP's interaction partners. This engineered cell line revealed that neural differentiation promotes a change in YAP interactors, including a dramatic increase in angiomotin (AMOT)interaction with YAP. AMOT regulates YAP localization during differentiation. AMOT expression increases during neural differentiation and leads to YAP nuclear exclusion. Our findings that AMOT-dependent regulation of YAP helps direct hPSC fate provide insight into the molecular mechanisms by which the microenvironment can induce neural differentiation. National Institutes of Health (Grant R01 GM049975) 2020-05-27T16:10:32Z 2020-05-27T16:10:32Z 2019-05 2017-10 2019-12-27T18:28:37Z Article http://purl.org/eprint/type/JournalArticle 2213-6711 https://hdl.handle.net/1721.1/125504 Zaltsman, Yefim et al. "Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells." Stem Cell Reports 12, 5 (May 2019): P869-877 © 2019 The Authors en http://dx.doi.org/10.1016/j.stemcr.2019.03.009 Stem Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Zaltsman, Yefim Masuko, Sayaka Bensen, Joshua J. Kiessling, Laura L Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title | Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title_full | Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title_fullStr | Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title_full_unstemmed | Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title_short | Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells |
| title_sort | angiomotin regulates yap localization during neural differentiation of human pluripotent stem cells |
| url | https://hdl.handle.net/1721.1/125504 |
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