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

RENZOVÁ, Tereza, Dáša BOHAČIAKOVÁ, Milan EŠNER, Veronika POSPÍŠILOVÁ, Tomáš BÁRTA, Aleš HAMPL and Lukáš ČAJÁNEK. Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells. STEM CELL REPORTS. CAMBRIDGE: CELL PRESS, 2018, vol. 11, No 4, p. 959-972. ISSN 2213-6711. Available from: https://dx.doi.org/10.1016/j.stemcr.2018.08.008.

Basic information

• Original name: Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
• Authors: RENZOVÁ, Tereza (203 Czech Republic, belonging to the institution), Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution), Milan EŠNER (203 Czech Republic, belonging to the institution), Veronika POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Aleš HAMPL (203 Czech Republic, belonging to the institution) and Lukáš ČAJÁNEK (203 Czech Republic, guarantor, belonging to the institution).
• Edition: STEM CELL REPORTS, CAMBRIDGE, CELL PRESS, 2018, 2213-6711.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10601 Cell biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 5.499
• RIV identification code: RIV/00216224:14110/18:00101379
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.stemcr.2018.08.008
• UT WoS: 000446691800011
• Keywords in English: PLK4-STIL module
• Tags: 14110517, CF CELLIM, podil, rivok

Abstract

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.

Links

• GJ15-18316Y, research and development project: Name: Úloha microRNA v řízení buněčného dělení a diferenciace lidských embryonálních kmenových buněk do neurálních kmenových buněk. (Acronym: miRNA v diferenciaci lidských EK buněk)

Investor: Czech Science Foundation

• GJ16-03269Y, research and development project: Name: Tau tubulin kináza 2 v ciliogenezi: molekulární mechanismy a funkční důsledky

Investor: Czech Science Foundation

• GJ16-24004Y, research and development project: Name: Indukce buněčné plasticity prostřednictvím modulace mikroRNA molekul: Nový přístup pro přeprogramování buněk

Investor: Czech Science Foundation

• GJ18-25429Y, research and development project: Name: Funkční studie mikroRNA u nerálních kmenových buněk v průběhu diferenciace

Investor: Czech Science Foundation

• LM2015062, research and development project: Name: Národní infrastruktura pro biologické a medicínské zobrazování

Investor: Ministry of Education, Youth and Sports of the CR

• MUNI/E/1310/2017, interní kód MU: Name: Finalizace manuskriptu "Acentrosomal divisions prevent self-renewal and trigger p53-dependent differentiation in human pluripotent stem cells".

Investor: Masaryk University, Promoting quality excellence

• MUNI/G/1131/2017, interní kód MU: Name: Transformative stem cell-based model of Alzheimer’s disease and advanced analytics to study the role of membrane lipids in the pathogenesis

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

• ROZV/24/LF/2016, interní kód MU: Name: LF - Příspěvek IP 2016

Investor: Ministry of Education, Youth and Sports of the CR

• ROZV/24/LF/2018, interní kód MU: Name: LF - Příspěvek na IP 2108

Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects

• ROZV/25/LF/2017, interní kód MU: Name: LF - Příspěvek na IP 2017

Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects