J 2018

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 et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.499

RIV identification code

RIV/00216224:14110/18:00101379

Organization unit

Faculty of Medicine

DOI

UT WoS

000446691800011

Keywords in English

PLK4-STIL module

Tags

Tags

International impact, Reviewed
Změněno: 14/11/2024 14:00, Mgr. Eva Dubská

Abstract

V originále

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
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
90062, large research infrastructures
Name: Czech-BioImaging