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Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells

Centrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module repres...

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Autores principales: Renzova, Tereza, Bohaciakova, Dasa, Esner, Milan, Pospisilova, Veronika, Barta, Tomas, Hampl, Ales, Cajanek, Lukas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178195/
https://www.ncbi.nlm.nih.gov/pubmed/30197118
http://dx.doi.org/10.1016/j.stemcr.2018.08.008
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author Renzova, Tereza
Bohaciakova, Dasa
Esner, Milan
Pospisilova, Veronika
Barta, Tomas
Hampl, Ales
Cajanek, Lukas
author_facet Renzova, Tereza
Bohaciakova, Dasa
Esner, Milan
Pospisilova, Veronika
Barta, Tomas
Hampl, Ales
Cajanek, Lukas
author_sort Renzova, Tereza
collection PubMed
description Centrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module represents a key element of centrosome duplication cycle. We analyzed consequences of inactivation of the module for early events of embryogenesis in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We demonstrate that blocking of PLK4 or STIL functions leads to centrosome loss followed by both p53-dependent and -independent defects, including prolonged cell divisions, upregulation of p53, chromosome instability, and, importantly, reduction of pluripotency markers and induction of differentiation. We show that the observed loss of key stem cells properties is connected to alterations in mitotic timing and protein turnover. In sum, our data define a link between centrosome, its regulators, and the control of pluripotency and differentiation in PSCs.
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spelling pubmed-61781952018-10-11 Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells Renzova, Tereza Bohaciakova, Dasa Esner, Milan Pospisilova, Veronika Barta, Tomas Hampl, Ales Cajanek, Lukas Stem Cell Reports Article Centrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module represents a key element of centrosome duplication cycle. We analyzed consequences of inactivation of the module for early events of embryogenesis in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We demonstrate that blocking of PLK4 or STIL functions leads to centrosome loss followed by both p53-dependent and -independent defects, including prolonged cell divisions, upregulation of p53, chromosome instability, and, importantly, reduction of pluripotency markers and induction of differentiation. We show that the observed loss of key stem cells properties is connected to alterations in mitotic timing and protein turnover. In sum, our data define a link between centrosome, its regulators, and the control of pluripotency and differentiation in PSCs. Elsevier 2018-09-06 /pmc/articles/PMC6178195/ /pubmed/30197118 http://dx.doi.org/10.1016/j.stemcr.2018.08.008 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Renzova, Tereza
Bohaciakova, Dasa
Esner, Milan
Pospisilova, Veronika
Barta, Tomas
Hampl, Ales
Cajanek, Lukas
Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title_full Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title_fullStr Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title_full_unstemmed Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title_short Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
title_sort inactivation of plk4-stil module prevents self-renewal and triggers p53-dependent differentiation in human pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178195/
https://www.ncbi.nlm.nih.gov/pubmed/30197118
http://dx.doi.org/10.1016/j.stemcr.2018.08.008
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