MEK and TGF-beta Inhibition Promotes Reprogramming without the
Use of Transcription Factor

J 2015

MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor

VRBSKÝ, Jan, Tamás TEREH, Sergiy KYRYLENKO, Petr DVOŘÁK, Lumír KREJČÍ et. al.

Basic information

Original name

MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor

Authors

VRBSKÝ, Jan (203 Czech Republic, belonging to the institution), Tamás TEREH (348 Hungary, belonging to the institution), Sergiy KYRYLENKO (246 Finland, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution) and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Plos one, San Francisco, Public Library of Science, 2015, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.057

RIV identification code

RIV/00216224:14110/15:00080987

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1371/journal.pone.0127739

UT WoS

000355700700073

Keywords in English

PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; SMALL-MOLECULE COMPOUNDS; PRIMORDIAL GERM-CELLS; SELF-RENEWAL; NEURONAL DIFFERENTIATION; PROGENITOR CELLS; MOUSE; INDUCTION; NANOG

Abstract

V originále

The possibility of replacing the originally discovered and widely used DNA reprogramming transcription factors is stimulating enormous effort to identify more effective compounds that would not alter the genetic information. Here, we describe the generation of induced pluripotent stem cells (iPSc) from head-derived primary culture of mouse embryonic cells using small chemical inhibitors of the MEK and TGF-beta pathways without delivery of exogenous transcription factors. These iPSc express standard pluripotency markers and retain their potential to differentiate into cells of all germ layers. Our data indicate that head-derived embryonic neural cells might have the reprogramming potential while neither the same primary cells cultivated over five passages in vitro nor a cell population derived from adult brain possesses this capacity. Our results reveal the potential for small molecules to functionally replace routinely used transcription factors and lift the veil on molecular regulation controlling pluripotency. The conditions described here could provide a platform upon which other genome non integrative and safer reprogramming processes could be developed. This work also shows novel potential for developing embryonic neural cells.

Links

EE2.3.20.0011, research and development project

Name: Centrum výzkumu pluripotentních buněk a nestability genomu

GAP207/12/2323, research and development project

Name: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Czech Science Foundation

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

NS10231, research and development project

Name: Neurální diferenciace u microRNA indukovaných pluripotentních kmenových buněk

Investor: Ministry of Health of the CR

SIGA549, interní kód MU

Name: METASTEM - Metabolická signalizace a energetická homeostáze u lidských embryonálních kmenových buněk (Acronym: METASTEM)

Investor: South-Moravian Region, Incoming grants

Citovat

VRBSKÝ, Jan, Tamás TEREH, Sergiy KYRYLENKO, Petr DVOŘÁK and Lumír KREJČÍ. MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor. Plos one. San Francisco: Public Library of Science, 2015, vol. 10, No 6, p. "e0127739", 16 pp. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0127739.

@article{1309636,
   author = {Vrbský, Jan and Tereh, Tamás and Kyrylenko, Sergiy and Dvořák, Petr and Krejčí, Lumír},
   article_location = {San Francisco},
   article_number = {6},
   doi = {http://dx.doi.org/10.1371/journal.pone.0127739},
   keywords = {PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; SMALL-MOLECULE COMPOUNDS; PRIMORDIAL GERM-CELLS; SELF-RENEWAL; NEURONAL DIFFERENTIATION; PROGENITOR CELLS; MOUSE; INDUCTION; NANOG},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor},
   volume = {10},
   year = {2015}
}

TY  - JOUR
ID  - 1309636
AU  - Vrbský, Jan - Tereh, Tamás - Kyrylenko, Sergiy - Dvořák, Petr - Krejčí, Lumír
PY  - 2015
TI  - MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor
JF  - Plos one
VL  - 10
IS  - 6
SP  - "e0127739"
EP  - "e0127739"
PB  - Public Library of Science
SN  - 19326203
KW  - PLURIPOTENT STEM-CELLS
KW  - HUMAN SOMATIC-CELLS
KW  - SMALL-MOLECULE COMPOUNDS
KW  - PRIMORDIAL GERM-CELLS
KW  - SELF-RENEWAL
KW  - NEURONAL DIFFERENTIATION
KW  - PROGENITOR CELLS
KW  - MOUSE
KW  - INDUCTION
KW  - NANOG
N2  - The possibility of replacing the originally discovered and widely used DNA reprogramming transcription factors is stimulating enormous effort to identify more effective compounds that would not alter the genetic information. Here, we describe the generation of induced pluripotent stem cells (iPSc) from head-derived primary culture of mouse embryonic cells using small chemical inhibitors of the MEK and TGF-beta pathways without delivery of exogenous transcription factors. These iPSc express standard pluripotency markers and retain their potential to differentiate into cells of all germ layers. Our data indicate that head-derived embryonic neural cells might have the reprogramming potential while neither the same primary cells cultivated over five passages in vitro nor a cell population derived from adult brain possesses this capacity. Our results reveal the potential for small molecules to functionally replace routinely used transcription factors and lift the veil on molecular regulation controlling pluripotency. The conditions described here could provide a platform upon which other genome non integrative and safer reprogramming processes could be developed. This work also shows novel potential for developing embryonic neural cells.
ER  -

VRBSKÝ, Jan, Tamás TEREH, Sergiy KYRYLENKO, Petr DVOŘÁK and Lumír KREJČÍ. MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor. \textit{Plos one}. San Francisco: Public Library of Science, 2015, vol.~10, No~6, p.~''e0127739'', 16 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0127739.

Detailed Information on Publication Record