Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

CEITEC Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic

CEITEC Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

CEITEC Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic National Centre for Biomolecular Research Faculty of Science Masaryk University Brno 625 00 Czech Republic

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno 625 00 Czech Republic

000      

00000naa a2200000 a 4500

001      

bmc20028774

003      

CZ-PrNML

005      

20210114155135.0

007      

ta

008      

210105s2019 xxk f 000 0|eng||

009      

AR

024    7_

$a 10.1038/s41598-019-52294-3 $2 doi

035    __

$a (PubMed)31673026

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a xxk

100    1_

$a Peskova, Lucie $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, 625 00, Czech Republic.

245    10

$a Oct4-mediated reprogramming induces embryonic-like microRNA expression signatures in human fibroblasts / $c L. Peskova, K. Cerna, J. Oppelt, M. Mraz, T. Barta,

520    9_

$a Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

650    _2

$a buněčné linie $7 D002460

650    12

$a techniky buněčného přeprogramování $7 D000067470

650    12

$a embryo savčí $7 D004622

650    _2

$a fibroblasty $x cytologie $x metabolismus $7 D005347

650    12

$a regulace genové exprese $7 D005786

650    _2

$a lidé $7 D006801

650    12

$a mikro RNA $x biosyntéza $x genetika $7 D035683

650    12

$a oktamerní transkripční faktor 3 $x biosyntéza $x genetika $7 D050814

655    _2

$a časopisecké články $7 D016428

655    _2

$a práce podpořená grantem $7 D013485

700    1_

$a Cerna, Katerina $u CEITEC-Central European Institute of Technology, Masaryk University, Brno, 625 00, Czech Republic.

700    1_

$a Oppelt, Jan $u CEITEC-Central European Institute of Technology, Masaryk University, Brno, 625 00, Czech Republic. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, 625 00, Czech Republic.

700    1_

$a Mraz, Marek $u CEITEC-Central European Institute of Technology, Masaryk University, Brno, 625 00, Czech Republic. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

700    1_

$a Barta, Tomas $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, 625 00, Czech Republic. tbarta@med.muni.cz.

773    0_

$w MED00182195 $t Scientific reports $x 2045-2322 $g Roč. 9, č. 1 (2019), s. 15759

856    41

$u https://pubmed.ncbi.nlm.nih.gov/31673026 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y a $z 0

990    __

$a 20210105 $b ABA008

991    __

$a 20210114155133 $b ABA008

999    __

$a ok $b bmc $g 1609109 $s 1119954

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2019 $b 9 $c 1 $d 15759 $e 20191031 $i 2045-2322 $m Scientific reports $n Sci Rep $x MED00182195

LZP    __

$a Pubmed-20210105