000063478 001__ 63478
000063478 005__ 20210121114537.0
000063478 0247_ $$2doi$$a10.1016/j.stemcr.2015.09.004
000063478 0248_ $$2sideral$$a103219
000063478 037__ $$aART-2015-103219
000063478 041__ $$aeng
000063478 100__ $$0(orcid)0000-0003-3982-1263$$aOrdovás, L
000063478 245__ $$aEfficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition
000063478 260__ $$c2015
000063478 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063478 5203_ $$aTools for rapid and efficient transgenesis in "safe harbor" loci in an isogenic context remain important to exploit the possibilities of human pluripotent stem cells (hPSCs). We created hPSC master cell lines suitable for FLPe recombinase-mediated cassette exchange (RMCE) in the AAVS1 locus that allow generation of transgenic lines within 15 days with 100% efficiency and without random integrations. Using RMCE, we successfully incorporated several transgenes useful for lineage identification, cell toxicity studies, and gene overexpression to study the hepatocyte lineage. However, we observed unexpected and variable transgene expression inhibition in vitro, due to DNA methylation and other unknown mechanisms, both in undifferentiated hESC and differentiating hepatocytes. Therefore, the AAVS1 locus cannot be considered a universally safe harbor locus for reliable transgene expression in vitro, and using it for transgenesis in hPSC will require careful assessment of the function of individual transgenes.
000063478 536__ $$9info:eu-repo/grantAgreement/ES/DGA/FMI048-08
000063478 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000063478 590__ $$a7.023$$b2015
000063478 591__ $$aCELL & TISSUE ENGINEERING$$b2 / 21 = 0.095$$c2015$$dQ1$$eT1
000063478 591__ $$aCELL BIOLOGY$$b30 / 187 = 0.16$$c2015$$dQ1$$eT1
000063478 592__ $$a5.578$$b2015
000063478 593__ $$aBiochemistry$$c2015$$dQ1
000063478 593__ $$aGenetics$$c2015$$dQ1
000063478 593__ $$aDevelopmental Biology$$c2015$$dQ1
000063478 593__ $$aCell Biology$$c2015$$dQ1
000063478 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063478 700__ $$aBoon, R
000063478 700__ $$aPistoni, M
000063478 700__ $$aChen, Y
000063478 700__ $$aWolfs, E
000063478 700__ $$aGuo, W
000063478 700__ $$aSambathkumar, R
000063478 700__ $$aBobis-Wozowicz, S
000063478 700__ $$aHelsen, N
000063478 700__ $$aVanhove, J
000063478 700__ $$aBerckmans, P
000063478 700__ $$aCai, Q
000063478 700__ $$aVanuytsel, K
000063478 700__ $$aEggermont, K
000063478 700__ $$aVanslembrouck, V
000063478 700__ $$aSchmidt, BZ
000063478 700__ $$aRaitano, S
000063478 700__ $$aVan Den Bosch, L
000063478 700__ $$aNahmias, Y
000063478 700__ $$aCathomen, T
000063478 700__ $$aStruys, T
000063478 700__ $$aVerfaillie, CM
000063478 773__ $$g5, 5 (2015), 918-931$$pStem cell rep.$$tStem cell reports$$x2213-6711
000063478 8564_ $$s4001903$$uhttps://zaguan.unizar.es/record/63478/files/texto_completo.pdf$$yVersión publicada
000063478 8564_ $$s123788$$uhttps://zaguan.unizar.es/record/63478/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063478 909CO $$ooai:zaguan.unizar.es:63478$$particulos$$pdriver
000063478 951__ $$a2021-01-21-11:14:27
000063478 980__ $$aARTICLE