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Article: An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming

TitleAn engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming
Authors
Issue Date25-Aug-2023
PublisherAmerican Association for the Advancement of Science
Citation
Science Advances, 2023, v. 9, n. 34 How to Cite?
Abstract

Advanced strategies to interconvert cell types provide promising avenues to model cellular pathologies and to develop therapies for neurological disorders. Yet, methods to directly transdifferentiate somatic cells into multipotent induced neural stem cells (iNSCs) are slow and inefficient, and it is unclear whether cells pass through a pluripotent state with full epigenetic reset. We report iNSC reprogramming from embryonic and aged mouse fibroblasts as well as from human blood using an engineered Sox17 (eSox17FNV). eSox17FNV efficiently drives iNSC reprogramming while Sox2 or Sox17 fail. eSox17FNV acquires the capacity to bind different protein partners on regulatory DNA to scan the genome more efficiently and has a more potent transactivation domain than Sox2. Lineage tracing and time-resolved transcriptomics show that emerging iNSCs do not transit through a pluripotent state. Our work distinguishes lineage from pluripotency reprogramming with the potential to generate more authentic cell models for aging-associated neurodegenerative diseases.


Persistent Identifierhttp://hdl.handle.net/10722/338224
ISSN
2023 Impact Factor: 11.7
2023 SCImago Journal Rankings: 4.483
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWeng, Mingxi-
dc.contributor.authorHu, Haoqing-
dc.contributor.authorGraus, Matthew S-
dc.contributor.authorTan, Daisylyn Senna-
dc.contributor.authorGao, Ya-
dc.contributor.authorRen, Shimiao-
dc.contributor.authorHo, Derek Hoi Hang-
dc.contributor.authorLanger, Jakob-
dc.contributor.authorHolzner, Markus-
dc.contributor.authorHuang, Yuhua-
dc.contributor.authorLing, Guang Sheng-
dc.contributor.authorLai, Cora Sau Wan-
dc.contributor.authorFrancois, Mathias-
dc.contributor.authorJauch, Ralf-
dc.date.accessioned2024-03-11T10:27:12Z-
dc.date.available2024-03-11T10:27:12Z-
dc.date.issued2023-08-25-
dc.identifier.citationScience Advances, 2023, v. 9, n. 34-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10722/338224-
dc.description.abstract<p>Advanced strategies to interconvert cell types provide promising avenues to model cellular pathologies and to develop therapies for neurological disorders. Yet, methods to directly transdifferentiate somatic cells into multipotent induced neural stem cells (iNSCs) are slow and inefficient, and it is unclear whether cells pass through a pluripotent state with full epigenetic reset. We report iNSC reprogramming from embryonic and aged mouse fibroblasts as well as from human blood using an engineered Sox17 (eSox17<sup>FNV</sup>). eSox17<sup>FNV</sup> efficiently drives iNSC reprogramming while Sox2 or Sox17 fail. eSox17<sup>FNV</sup> acquires the capacity to bind different protein partners on regulatory DNA to scan the genome more efficiently and has a more potent transactivation domain than Sox2. Lineage tracing and time-resolved transcriptomics show that emerging iNSCs do not transit through a pluripotent state. Our work distinguishes lineage from pluripotency reprogramming with the potential to generate more authentic cell models for aging-associated neurodegenerative diseases.<br></p>-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAn engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming-
dc.typeArticle-
dc.identifier.doi10.1126/sciadv.adh2501-
dc.identifier.scopuseid_2-s2.0-85168574002-
dc.identifier.volume9-
dc.identifier.issue34-
dc.identifier.eissn2375-2548-
dc.identifier.isiWOS:001053144500012-
dc.identifier.issnl2375-2548-

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