000063474 001__ 63474
000063474 005__ 20190709135542.0
000063474 0247_ $$2doi$$a10.1371/journal.pone.0186884
000063474 0248_ $$2sideral$$a103208
000063474 037__ $$aART-2017-103208
000063474 041__ $$aeng
000063474 100__ $$aPistoni, M
000063474 245__ $$aDynamic regulation of EZH2 from HPSc to hepatocyte-like cell fate
000063474 260__ $$c2017
000063474 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063474 5203_ $$aCurrently, drug metabolization and toxicity studies rely on the use of primary human hepatocytes and hepatoma cell lines, which both have conceivable limitations. Human pluripotent stem cell (hPSC)—derived hepatocyte-like cells (HLCs) are an alternative and valuable source of hepatocytes that can overcome these limitations. EZH2 (enhancer of zeste homolog 2), a transcriptional repressor of the polycomb repressive complex 2 (PRC2), may play an important role in hepatocyte development, but its role during in vitro hPSC-HLC differentiation has not yet been assessed. We here demonstrate dynamic regulation of EZH2 during hepatic differentiation of hPSC. To enhance EZH2 expression, we inducibly overexpressed EZH2 between d0 and d8, demonstrating a significant improvement in definitive endoderm formation, and improved generation of HLCs. Despite induction of EZH2 overexpression until d8, EZH2 transcript and protein levels decreased from d4 onwards, which might be caused by expression of microRNAs predicted to inhibit EZH2 expression. In conclusion, our studies demonstrate that EZH2 plays a role in endoderm formation and hepatocyte differentiation, but its expression is tightly post-transcriptionally regulated during this process
000063474 536__ $$9info:eu-repo/grantAgreement/ES/DGA/FMI048-08
000063474 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063474 590__ $$a2.766$$b2017
000063474 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 64 = 0.234$$c2017$$dQ1$$eT1
000063474 592__ $$a1.164$$b2017
000063474 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2017$$dQ1
000063474 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000063474 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000063474 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063474 700__ $$aHelsen, N
000063474 700__ $$aVanhove, J
000063474 700__ $$aBoon, R
000063474 700__ $$aXu, Z
000063474 700__ $$0(orcid)0000-0003-3982-1263$$aOrdovas, L
000063474 700__ $$aVerfaillie, CM
000063474 773__ $$g12, 11 (2017), e0186884 [19pp]$$pPLoS One$$tPloS one$$x1932-6203
000063474 8564_ $$s2113681$$uhttps://zaguan.unizar.es/record/63474/files/texto_completo.pdf$$yVersión publicada
000063474 8564_ $$s104787$$uhttps://zaguan.unizar.es/record/63474/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063474 909CO $$ooai:zaguan.unizar.es:63474$$particulos$$pdriver
000063474 951__ $$a2019-07-09-12:07:52
000063474 980__ $$aARTICLE