id:"swepub:oai:prod.swepub.kib.ki.se:139155517"
Search: id:"swepub:oai:prod.swepub.kib.ki.se:139155517" > Ectopic hTERT expre...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Wang, SY (author)
Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model
- Article/chapterEnglish2018
Publisher, publication year, extent ...
- 2018-09-11
- Springer Science and Business Media LLC,2018
Numbers
- LIBRIS-ID:oai:prod.swepub.kib.ki.se:139155517
- http://kipublications.ki.se/Default.aspx?queryparsed=id:139155517URI
- https://doi.org/10.1038/s41419-018-0948-4DOI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- The induced pluripotent stem cell (iPSC) technology has provided a unique opportunity to develop disease-specific models and personalized treatment for genetic disorders, and is well suitable for the study of Werner syndrome (WS), an autosomal recessive disease with adult onset of premature aging caused by mutations in the RecQ like helicase (WRN) gene. WS-derived fibroblasts were previously shown to be able to generate iPSCs; however, it remains elusive how WS-derived iPSCs behave and whether they are able to mimic the disease-specific phenotype. The present study was designed to address these issues. Unexpectedly, we found that a specific WS fibroblast line of homozygous truncation mutation was difficult to be reprogrammed by using the Yamanaka factors even under hypoxic conditions due to their defect in induction of hTERT, the catalytic unit of telomerase. Ectopic expression of hTERT restores the ability of this WS fibroblast line to form iPSCs, although with a low efficiency. To examine the phenotype of WRN-deficient pluripotent stem cells, we also generated WRN knockout human embryonic stem (ES) cells by using the CRISPR/Cas9 method. The iPSCs derived from WS-hTERT cells and WRN-/- ESCs are fully pluripotent, express pluripotent markers and can differentiate into three germ layer cells; however, WS-iPSCs and WRN-/- ESCs show S phase defect in cell cycle progression. Moreover, WS-iPSCs and WRN-/- ESCs, like WS patient-derived fibroblasts, remain hypersensitive to topoisomerase inhibitors. Collectively, WS-derived iPSCs and WRN-/- ESCs mimic the intrinsic disease phenotype, which may serve as a suitable disease model, whereas not be good for a therapeutic purpose without gene correction.
Added entries (persons, corporate bodies, meetings, titles ...)
- Liu, ZF (author)
- Ye, YX (author)
- Li, BNKarolinska Institutet (author)
- Liu, TT (author)
- Zhang, WQ (author)
- Liu, GH (author)
- Zhang, YA (author)
- Qu, J (author)
- Xu, DWKarolinska Institutet (author)
- Chen, ZG (author)
- Karolinska Institutet (creator_code:org_t)
Related titles
- In:Cell death & disease: Springer Science and Business Media LLC9:9, s. 923-2041-4889
Internet link
Find in a library
- Cell death & disease (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Wang, SY
- Liu, ZF
- Ye, YX
- Li, BN
- Liu, TT
- Zhang, WQ
- show more...
- Liu, GH
- Zhang, YA
- Qu, J
- Xu, DW
- Chen, ZG
- show less...
- Articles in the publication
- Cell death & dis ...
- By the university
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
