title: Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor.
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.
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shahbazi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
authors.forename: Sharif
authors.initials: S
authors.lastname: Moradi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Nemati
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Satarian
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Basiri
authors.affiliation: Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran 1665659911, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Gourabi
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne 50931, Germany.
authors.forename: Narges
authors.initials: N
authors.lastname: Zare Mehrjardi
authors.affiliation: Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn 53115, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Günther
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander-University of Erlangen- Nürnberg, Erlangen 91054, Germany; Institute of Physiology, RWTH, Aachen University, Aachen 52074, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Lampert
authors.affiliation: Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn 53115, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Händler
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne 50931, Germany.
authors.forename: Firuze Fulya
authors.initials: FF
authors.lastname: Hatay
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander-University of Erlangen- Nürnberg, Erlangen 91054, Germany; IZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne 50931, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Molcanyi
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne 50931, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn 53115, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne 50931, Germany. Electronic address: tomo.saric@uni-koeln.de.
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran 1461968151, Iran. Electronic address: baharvand@royaninstitute.org.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D000066673:Cell Self Renewal / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D011923:Rats, Nude; D033581:Stem Cell Transplantation / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: C472572:Evi3 protein, mouse; D014157:Transcription Factors