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http://hdl.handle.net/1942/20238
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DC Field | Value | Language |
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dc.contributor.author | Ordovás, Laura | - |
dc.contributor.author | Boon, Ruben | - |
dc.contributor.author | Pistoni, Mariaelena | - |
dc.contributor.author | Chen, Yemiao | - |
dc.contributor.author | WOLFS, Esther | - |
dc.contributor.author | Guo, Wenting | - |
dc.contributor.author | Sambathkumar, Rangarajan | - |
dc.contributor.author | Bobis-Wozowicz, Sylwia | - |
dc.contributor.author | Helsen, Nicky | - |
dc.contributor.author | Vanhove, Jolien | - |
dc.contributor.author | Berckmans, Pieter | - |
dc.contributor.author | Cai, Qing | - |
dc.contributor.author | Vanuytsel, Kim | - |
dc.contributor.author | Eggermont, Kristel | - |
dc.contributor.author | Vanslembrouck, Veerle | - |
dc.contributor.author | Schmidt, Béla Z. | - |
dc.contributor.author | Raitano, Susanna | - |
dc.contributor.author | Van den Bosch, Ludo | - |
dc.contributor.author | Nahmias, Yaakov | - |
dc.contributor.author | Cathomen, Toni | - |
dc.contributor.author | STRUYS, Tom | - |
dc.contributor.author | Verfaillie, Catherine M. | - |
dc.date.accessioned | 2016-01-14T08:52:09Z | - |
dc.date.available | 2016-01-14T08:52:09Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Stem Cell Reports, 5 (5), p. 918-931 | - |
dc.identifier.issn | 2213-6711 | - |
dc.identifier.uri | http://hdl.handle.net/1942/20238 | - |
dc.description.abstract | Tools 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. | - |
dc.description.sponsorship | L.O. was funded by IWT/OZM/090838, IACS BPAMER3/08/04, and Government of Aragon FMI048/08; M.P. by FWO 1288714N; and R.S. by the Dutch Diabetes Foundation. R.B., N.H., J.V., K.C., and Q.C. were supported by IWT fellowships SB-121393, SB-121396, SB-101230, SB-091228, and SB-093228, respectively. B.Z.S. was financed by FP7-PEOPLE-2011-IIF (Proposal No. 298785) and W.G. by the China Scholarship Council. S.B.-W. and T.C. were supported by the FP7-HEMIBIO (266777). Funding to C.M.V. was from FWO G.0667.07 and G.0975.11; KU Leuven (EIW-B4855-EF/05/11, ETH-C1900-PF, EME-C2161-GOA/11/012), IWT-HEPSTEM, BELSPO-IUAP-DEVREPAIR, FP7-HEMIBIO (266777). We thank Prof. P. Collas and Dr. B. Izzi for their discussions related to the DNA methylation studies; Dr. D. Franckaert, Dr. S. Schlenner, and Dr. A. Van Nieuwenhuijze for their availability to operate the sorter as well as M. Welters and R. Van Rossom for technical assistance. | - |
dc.language.iso | en | - |
dc.rights | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | - |
dc.title | Efficient recombinase-mediated cassette exchange in hPSCs to study the hepatocyte lineage reveals AAVS1 locus-mediated transgene inhibition | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 931 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 918 | - |
dc.identifier.volume | 5 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Correspondence: laura.ordovas@med.kuleuven.be or lordovas@unizar.es (L.O.), catherine.verfaillie@med.kuleuven.be (C.M.V.) | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1016/j.stemcr.2015.09.004 | - |
dc.identifier.isi | 000364991000021 | - |
item.validation | ecoom 2016 | - |
item.contributor | Ordovás, Laura | - |
item.contributor | Boon, Ruben | - |
item.contributor | Pistoni, Mariaelena | - |
item.contributor | Chen, Yemiao | - |
item.contributor | WOLFS, Esther | - |
item.contributor | Guo, Wenting | - |
item.contributor | Sambathkumar, Rangarajan | - |
item.contributor | Bobis-Wozowicz, Sylwia | - |
item.contributor | Helsen, Nicky | - |
item.contributor | Vanhove, Jolien | - |
item.contributor | Berckmans, Pieter | - |
item.contributor | Cai, Qing | - |
item.contributor | Vanuytsel, Kim | - |
item.contributor | Eggermont, Kristel | - |
item.contributor | Vanslembrouck, Veerle | - |
item.contributor | Schmidt, Béla Z. | - |
item.contributor | Raitano, Susanna | - |
item.contributor | Van den Bosch, Ludo | - |
item.contributor | Nahmias, Yaakov | - |
item.contributor | Cathomen, Toni | - |
item.contributor | STRUYS, Tom | - |
item.contributor | Verfaillie, Catherine M. | - |
item.accessRights | Open Access | - |
item.fullcitation | Ordovás, Laura; Boon, Ruben; Pistoni, Mariaelena; Chen, Yemiao; WOLFS, Esther; Guo, Wenting; Sambathkumar, Rangarajan; Bobis-Wozowicz, Sylwia; Helsen, Nicky; Vanhove, Jolien; Berckmans, Pieter; Cai, Qing; Vanuytsel, Kim; Eggermont, Kristel; Vanslembrouck, Veerle; Schmidt, Béla Z.; Raitano, Susanna; Van den Bosch, Ludo; Nahmias, Yaakov; Cathomen, Toni; STRUYS, Tom & Verfaillie, Catherine M. (2015) Efficient recombinase-mediated cassette exchange in hPSCs to study the hepatocyte lineage reveals AAVS1 locus-mediated transgene inhibition. In: Stem Cell Reports, 5 (5), p. 918-931. | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 2213-6711 | - |
crisitem.journal.eissn | 2213-6711 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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2015_Ordovas_SCRep.pdf | Published version | 3.91 MB | Adobe PDF | View/Open |
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