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Identification of embryonic neural plate border stem cells and their generation by direct reprogramming from adult human blood cells

We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage diff...

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Main Authors: Thier, Marc Christian (Author) , Pinna, Roberta (Author) , García-González, Diego (Author) , Assenov, Yassen (Author) , Milsom, Michael (Author) , Jauch, Anna (Author) , Utikal, Jochen (Author) , Herrmann, Carl (Author) , Monyer, Hannah (Author) , Trumpp, Andreas (Author)
Format: Article (Journal)
Language:English
Published: December 20, 2018
In: Cell stem cell
Year: 2019, Volume: 24, Issue: 1, Pages: 166-182.e13
ISSN:1875-9777
DOI:10.1016/j.stem.2018.11.015
Online Access:Resolving-System, Volltext: http://dx.doi.org/10.1016/j.stem.2018.11.015
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1934590918305514
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Author Notes:Marc Christian Thier, Oliver Hommerding, Jasper Panten, Roberta Pinna, Diego García-González, Thomas Berger, Philipp Wörsdörfer, Yassen Assenov, Roberta Scognamiglio, Adriana Przybylla, Paul Kaschutnig, Lisa Becker, Michael D. Milsom, Anna Jauch, Jochen Utikal, Carl Herrmann, Hannah Monyer, Frank Edenhofer, Andreas Trumpp
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Summary:We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.
Item Description:Gesehen am 24.01.2019
Physical Description:Online Resource
ISSN:1875-9777
DOI:10.1016/j.stem.2018.11.015

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