Shahbazi, Ebrahim, Moradi, Sharif ORCID: 0000-0002-2935-983X, Nemati, Shiva, Satarian, Leila ORCID: 0000-0002-5068-5031, Basiri, Mohsen ORCID: 0000-0003-2512-7641, Gourabi, Hamid, Mehrjardi, Narges Zare, Guenther, Patrick, Lampert, Angelika ORCID: 0000-0001-6319-6272, Haendler, Kristian, Hatay, Firuze Fulya, Schmidt, Diana, Molcanyi, Marek, Hescheler, Juergen, Schultze, Joachim L., Saric, Tomo ORCID: 0000-0001-8344-1095 and Baharvand, Hossein (2016). Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor. Stem Cell Rep., 6 (4). S. 539 - 552. CAMBRIDGE: CELL PRESS. ISSN 2213-6711

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Abstract

Direct conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shahbazi, EbrahimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moradi, SharifUNSPECIFIEDorcid.org/0000-0002-2935-983XUNSPECIFIED
Nemati, ShivaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Satarian, LeilaUNSPECIFIEDorcid.org/0000-0002-5068-5031UNSPECIFIED
Basiri, MohsenUNSPECIFIEDorcid.org/0000-0003-2512-7641UNSPECIFIED
Gourabi, HamidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehrjardi, Narges ZareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lampert, AngelikaUNSPECIFIEDorcid.org/0000-0001-6319-6272UNSPECIFIED
Haendler, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hatay, Firuze FulyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molcanyi, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze, Joachim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saric, TomoUNSPECIFIEDorcid.org/0000-0001-8344-1095UNSPECIFIED
Baharvand, HosseinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-278708
DOI: 10.1016/j.stemcr.2016.02.013
Journal or Publication Title: Stem Cell Rep.
Volume: 6
Number: 4
Page Range: S. 539 - 552
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2213-6711
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DIRECT LINEAGE CONVERSION; FUNCTIONAL-NEURONS; DEFINED FACTORS; MOUSE; DIFFERENTIATION; INTEGRATION; PROGENITORS; GENERATION; FATEMultiple languages
Cell & Tissue Engineering; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27870

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