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| 001 | 285483 | ||
| 005 | 20260310095827.0 | ||
| 024 | 7 | _ | |a 10.1016/j.stem.2026.01.007 |2 doi |
| 024 | 7 | _ | |a pmid:41690310 |2 pmid |
| 024 | 7 | _ | |a 1934-5909 |2 ISSN |
| 024 | 7 | _ | |a 1875-9777 |2 ISSN |
| 037 | _ | _ | |a DZNE-2026-00259 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Uenaka, Takeshi |b 0 |
| 245 | _ | _ | |a Prevention of transgene silencing during human pluripotent stem cell differentiation. |
| 260 | _ | _ | |a Amsterdam [u.a.] |c 2026 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1773133032_12940 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Transgenes 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. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
| 536 | _ | _ | |a 351 - Brain Function (POF4-351) |0 G:(DE-HGF)POF4-351 |c POF4-351 |f POF IV |x 1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a PiggyBac vector |2 Other |
| 650 | _ | 7 | |a UCOE |2 Other |
| 650 | _ | 7 | |a WPRE |2 Other |
| 650 | _ | 7 | |a chromatin insulator |2 Other |
| 650 | _ | 7 | |a human pluripotent stem cells |2 Other |
| 650 | _ | 7 | |a microglia |2 Other |
| 650 | _ | 7 | |a neuron |2 Other |
| 650 | _ | 7 | |a promoter activity |2 Other |
| 650 | _ | 7 | |a safe harbor locus |2 Other |
| 650 | _ | 7 | |a transgene silencing |2 Other |
| 650 | _ | 7 | |a ubiquitous chromatin opening element |2 Other |
| 650 | _ | 7 | |a woodchuck hepatitis posttranscriptional regulatory element |2 Other |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Cell Differentiation: genetics |2 MeSH |
| 650 | _ | 2 | |a Transgenes: genetics |2 MeSH |
| 650 | _ | 2 | |a Pluripotent Stem Cells: cytology |2 MeSH |
| 650 | _ | 2 | |a Pluripotent Stem Cells: metabolism |2 MeSH |
| 650 | _ | 2 | |a Gene Silencing |2 MeSH |
| 650 | _ | 2 | |a Promoter Regions, Genetic: genetics |2 MeSH |
| 650 | _ | 2 | |a Genetic Vectors: genetics |2 MeSH |
| 650 | _ | 2 | |a Neurons: cytology |2 MeSH |
| 650 | _ | 2 | |a Neurons: metabolism |2 MeSH |
| 700 | 1 | _ | |a Napole, Alan |b 1 |
| 700 | 1 | _ | |a Saha, Aninda Dibya |b 2 |
| 700 | 1 | _ | |a Sun, Duo |b 3 |
| 700 | 1 | _ | |a Singavarapu, Angelina |b 4 |
| 700 | 1 | _ | |a Calzada, Elizabeth |b 5 |
| 700 | 1 | _ | |a Chen, Jiahui |b 6 |
| 700 | 1 | _ | |a Erlebach, Lena |0 P:(DE-2719)9000542 |b 7 |u dzne |
| 700 | 1 | _ | |a McQuade, Amanda |b 8 |
| 700 | 1 | _ | |a Ramos, Daniel M |b 9 |
| 700 | 1 | _ | |a Rigamonti, Alessandra |b 10 |
| 700 | 1 | _ | |a Salazar, Lisa |b 11 |
| 700 | 1 | _ | |a Samelson, Avi J |b 12 |
| 700 | 1 | _ | |a Sedov, Kamilla |b 13 |
| 700 | 1 | _ | |a Welsh, Natalie J |b 14 |
| 700 | 1 | _ | |a Wild, Katleen |0 P:(DE-2719)2811762 |b 15 |u dzne |
| 700 | 1 | _ | |a Wu, Qianxin |b 16 |
| 700 | 1 | _ | |a Arenas, Ernest |b 17 |
| 700 | 1 | _ | |a Bassett, Andrew R |b 18 |
| 700 | 1 | _ | |a Kampmann, Martin |b 19 |
| 700 | 1 | _ | |a Kronenberg-Versteeg, Deborah |0 P:(DE-2719)9001451 |b 20 |u dzne |
| 700 | 1 | _ | |a Merkle, Florian T |b 21 |
| 700 | 1 | _ | |a Schüle, Birgitt |b 22 |
| 700 | 1 | _ | |a Thompson, Leslie M |b 23 |
| 700 | 1 | _ | |a Skarnes, William C |b 24 |
| 700 | 1 | _ | |a Ward, Michael E |b 25 |
| 700 | 1 | _ | |a Wernig, Marius |b 26 |
| 773 | _ | _ | |a 10.1016/j.stem.2026.01.007 |g Vol. 33, no. 3, p. 517 - 530.e8 |0 PERI:(DE-600)2375356-0 |n 3 |p 517 - 530.e8 |t Cell stem cell |v 33 |y 2026 |x 1934-5909 |
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