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000285483 037__ $$aDZNE-2026-00259
000285483 041__ $$aEnglish
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000285483 1001_ $$aUenaka, Takeshi$$b0
000285483 245__ $$aPrevention of transgene silencing during human pluripotent stem cell differentiation.
000285483 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2026
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000285483 520__ $$aTransgenes are often silenced upon differentiation of pluripotent stem cells using conventional expression systems. Here, we developed the TK4 PiggyBac vector to conduct a comparative analysis to evaluate the impact of various promoters, transcriptional regulatory elements, insulators, and genomic integration sites on transgene silencing during neuronal differentiation. Our findings reveal that specific combinations of CAG and Ubc promoters with the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) can prevent transgene silencing during differentiation, whereas chromatin insulators have less impact on sustained expression. Three novel safe harbor loci, distant from known genes, as well as the citrate lyase beta-like (CLYBL) locus, similarly support the prevention of transgene silencing. Remarkably, the TK4 vector showed complete resistance to silencing across various neuronal and microglial differentiation protocols, as independently confirmed by seven laboratories. This construct will be highly useful for assays requiring stable transgene expression during differentiation and holds potential for broad applications in various research fields.
000285483 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000285483 650_7 $$2Other$$aPiggyBac vector
000285483 650_7 $$2Other$$aUCOE
000285483 650_7 $$2Other$$aWPRE
000285483 650_7 $$2Other$$achromatin insulator
000285483 650_7 $$2Other$$ahuman pluripotent stem cells
000285483 650_7 $$2Other$$amicroglia
000285483 650_7 $$2Other$$aneuron
000285483 650_7 $$2Other$$apromoter activity
000285483 650_7 $$2Other$$asafe harbor locus
000285483 650_7 $$2Other$$atransgene silencing
000285483 650_7 $$2Other$$aubiquitous chromatin opening element
000285483 650_7 $$2Other$$awoodchuck hepatitis posttranscriptional regulatory element
000285483 650_2 $$2MeSH$$aHumans
000285483 650_2 $$2MeSH$$aCell Differentiation: genetics
000285483 650_2 $$2MeSH$$aTransgenes: genetics
000285483 650_2 $$2MeSH$$aPluripotent Stem Cells: cytology
000285483 650_2 $$2MeSH$$aPluripotent Stem Cells: metabolism
000285483 650_2 $$2MeSH$$aGene Silencing
000285483 650_2 $$2MeSH$$aPromoter Regions, Genetic: genetics
000285483 650_2 $$2MeSH$$aGenetic Vectors: genetics
000285483 650_2 $$2MeSH$$aNeurons: cytology
000285483 650_2 $$2MeSH$$aNeurons: metabolism
000285483 7001_ $$aNapole, Alan$$b1
000285483 7001_ $$aSaha, Aninda Dibya$$b2
000285483 7001_ $$aSun, Duo$$b3
000285483 7001_ $$aSingavarapu, Angelina$$b4
000285483 7001_ $$aCalzada, Elizabeth$$b5
000285483 7001_ $$aChen, Jiahui$$b6
000285483 7001_ $$0P:(DE-2719)9000542$$aErlebach, Lena$$b7$$udzne
000285483 7001_ $$aMcQuade, Amanda$$b8
000285483 7001_ $$aRamos, Daniel M$$b9
000285483 7001_ $$aRigamonti, Alessandra$$b10
000285483 7001_ $$aSalazar, Lisa$$b11
000285483 7001_ $$aSamelson, Avi J$$b12
000285483 7001_ $$aSedov, Kamilla$$b13
000285483 7001_ $$aWelsh, Natalie J$$b14
000285483 7001_ $$0P:(DE-2719)2811762$$aWild, Katleen$$b15$$udzne
000285483 7001_ $$aWu, Qianxin$$b16
000285483 7001_ $$aArenas, Ernest$$b17
000285483 7001_ $$aBassett, Andrew R$$b18
000285483 7001_ $$aKampmann, Martin$$b19
000285483 7001_ $$0P:(DE-2719)9001451$$aKronenberg-Versteeg, Deborah$$b20$$udzne
000285483 7001_ $$aMerkle, Florian T$$b21
000285483 7001_ $$aSchüle, Birgitt$$b22
000285483 7001_ $$aThompson, Leslie M$$b23
000285483 7001_ $$aSkarnes, William C$$b24
000285483 7001_ $$aWard, Michael E$$b25
000285483 7001_ $$aWernig, Marius$$b26
000285483 773__ $$0PERI:(DE-600)2375356-0$$a10.1016/j.stem.2026.01.007$$gVol. 33, no. 3, p. 517 - 530.e8$$n3$$p517 - 530.e8$$tCell stem cell$$v33$$x1934-5909$$y2026
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