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Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells

Although the differentiation of pluripotent cells in embryonic stem cells (ESCs) is often associated with protein kinase-mediated signaling pathways and Tousled-like kinase 1 (Tlk1) is required for development in several species, the role of Tlk1 in ESC function remains unclear. Here, we used mouse...

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Autores principales: Lee, Jina, Kim, Min Seong, Park, Su Hyung, Jang, Yeun Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762884/
https://www.ncbi.nlm.nih.gov/pubmed/29321513
http://dx.doi.org/10.1038/s41598-017-18628-9
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author Lee, Jina
Kim, Min Seong
Park, Su Hyung
Jang, Yeun Kyu
author_facet Lee, Jina
Kim, Min Seong
Park, Su Hyung
Jang, Yeun Kyu
author_sort Lee, Jina
collection PubMed
description Although the differentiation of pluripotent cells in embryonic stem cells (ESCs) is often associated with protein kinase-mediated signaling pathways and Tousled-like kinase 1 (Tlk1) is required for development in several species, the role of Tlk1 in ESC function remains unclear. Here, we used mouse ESCs to study the function of Tlk1 in pluripotent cells. The knockdown (KD)-based Tlk1-deficient cells showed that Tlk1 is not essential for ESC self-renewal in an undifferentiated state. However, Tlk1-KD cells formed irregularly shaped embryoid bodies and induced resistance to differentiation cues, indicating their failure to differentiate into an embryoid body. Consistent with their failure to differentiate, Tlk1-KD cells failed to downregulate the expression of undifferentiated cell markers including Oct4, Nanog, and Sox2 during differentiation, suggesting a negative role of Tlk1. Interestingly, Tlk1 overexpression sufficiently downregulated the expression of core pluripotency factors possibly irrespective of its kinase activity, thereby leading to a partial loss of self-renewal ability even in an undifferentiated state. Moreover, Tlk1 overexpression caused severe growth defects and G(2)/M phase arrest as well as apoptosis. Collectively, our data suggest that Tlk1 negatively regulates the expression of pluripotency factors, thereby contributing to the scheduled differentiation of mouse ESCs.
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spelling pubmed-57628842018-01-17 Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells Lee, Jina Kim, Min Seong Park, Su Hyung Jang, Yeun Kyu Sci Rep Article Although the differentiation of pluripotent cells in embryonic stem cells (ESCs) is often associated with protein kinase-mediated signaling pathways and Tousled-like kinase 1 (Tlk1) is required for development in several species, the role of Tlk1 in ESC function remains unclear. Here, we used mouse ESCs to study the function of Tlk1 in pluripotent cells. The knockdown (KD)-based Tlk1-deficient cells showed that Tlk1 is not essential for ESC self-renewal in an undifferentiated state. However, Tlk1-KD cells formed irregularly shaped embryoid bodies and induced resistance to differentiation cues, indicating their failure to differentiate into an embryoid body. Consistent with their failure to differentiate, Tlk1-KD cells failed to downregulate the expression of undifferentiated cell markers including Oct4, Nanog, and Sox2 during differentiation, suggesting a negative role of Tlk1. Interestingly, Tlk1 overexpression sufficiently downregulated the expression of core pluripotency factors possibly irrespective of its kinase activity, thereby leading to a partial loss of self-renewal ability even in an undifferentiated state. Moreover, Tlk1 overexpression caused severe growth defects and G(2)/M phase arrest as well as apoptosis. Collectively, our data suggest that Tlk1 negatively regulates the expression of pluripotency factors, thereby contributing to the scheduled differentiation of mouse ESCs. Nature Publishing Group UK 2018-01-10 /pmc/articles/PMC5762884/ /pubmed/29321513 http://dx.doi.org/10.1038/s41598-017-18628-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lee, Jina
Kim, Min Seong
Park, Su Hyung
Jang, Yeun Kyu
Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title_full Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title_fullStr Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title_full_unstemmed Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title_short Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
title_sort tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762884/
https://www.ncbi.nlm.nih.gov/pubmed/29321513
http://dx.doi.org/10.1038/s41598-017-18628-9
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