Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a

Nature Communications
Dongchang XiaoMengqing Xiang

Abstract

Induced neural stem cells (iNSCs) reprogrammed from somatic cells have great potentials in cell replacement therapies and in vitro modeling of neural diseases. Direct conversion of fibroblasts into iNSCs has been shown to depend on a couple of key neural progenitor transcription factors (TFs), raising the question of whether such direct reprogramming can be achieved by non-neural progenitor TFs. Here we report that the non-neural progenitor TF Ptf1a alone is sufficient to directly reprogram mouse and human fibroblasts into self-renewable iNSCs capable of differentiating into functional neurons, astrocytes and oligodendrocytes, and improving cognitive dysfunction of Alzheimer's disease mouse models when transplanted. The reprogramming activity of Ptf1a depends on its Notch-independent interaction with Rbpj which leads to subsequent activation of expression of TF genes and Notch signaling required for NSC specification, self-renewal, and homeostasis. Together, our data identify a non-canonical and safer approach to establish iNSCs for research and therapeutic purposes.

References

Oct 10, 1998·Journal of Virology·T DullL Naldini
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·S UrlingerW Hillen
Aug 20, 2002·Nature Genetics·Yoshiya KawaguchiChristopher V E Wright
Sep 2, 2003·Neuron·Victoria GrahamLarysa Pevny
Oct 1, 2003·Nature Neuroscience·Magdalena BylundJonas Muhr
Nov 16, 2004·Nature Genetics·Gabrielle S SellickRichard S Houlston
Jan 6, 2005·Molecular and Cellular Biology·George Steele-PerkinsRichard M Gronostajski
Aug 10, 2005·PLoS Biology·Luciano ContiAustin Smith
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 1, 2006·Development·Yoshio FujitaniChristopher V E Wright
Jan 20, 2007·Genes, Brain, and Behavior·R S ReisererM P McDonald
Apr 5, 2007·Nature Protocols·Insa S SchroederAnna M Wobus
Apr 5, 2007·Nature Protocols·Robert M J Deacon
Oct 20, 2007·Nature Protocols·Melissa S ClineGary D Bader
Feb 8, 2008·Trends in Neurosciences·Jia-Yi LiPatrik Brundin
Jun 4, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Paolo CappellaJürgen Moll
Mar 7, 2009·Methods in Molecular Biology·Alexander Pfeifer, Andreas Hofmann
Apr 7, 2009·Cell·Shinya Yamanaka
May 6, 2009·Stem Cells·Dong Wook HanHans R Schöler
Apr 17, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Patrick S WesternAndrew H Sinclair
Jul 14, 2010·Cell Stem Cell·Xiaoqing ZhangSu-Chun Zhang
Sep 10, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kangxin JinMengqing Xiang
Apr 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Janghwan KimSheng Ding
Jan 18, 2012·Oncotarget·Giulia PiazziLuigi Ricciardiello

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Citations

Jan 30, 2019·Nature Neuroscience·Rebecca M MartonSergiu P Pașca
Apr 12, 2019·Frontiers in Neuroscience·Gaia ColasanteVania Broccoli
Nov 25, 2018·Cellular and Molecular Life Sciences : CMLS·Kangxin Jin, Mengqing Xiang
May 1, 2019·Pharmaceuticals·Inês M PereiraNuno A Silva
Feb 29, 2020·Stem Cells and Development·Donghui LiuXin-Fu Zhou
Apr 14, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kenichi Horisawa, Atsushi Suzuki
Dec 10, 2020·Development·Nikolaos Konstantinides, Claude Desplan
Nov 19, 2020·Diseases·Irene Villalón-GarcíaJosé Antonio Sánchez-Alcázar
Apr 30, 2021·Neurochemistry International·Emily M A LewisKristen L Kroll
May 15, 2021·Cell & Bioscience·Tianyuan Shi, Martin Cheung
Jul 4, 2021·The International Journal of Neuropsychopharmacology·Jakob UnterholznerRupert Lanzenberger
Sep 10, 2020·Journal of Medical Genetics·Yan ZhangXiongJian Luo
Oct 22, 2021·Frontiers in Cell and Developmental Biology·Dongchang XiaoMengqing Xiang
Nov 5, 2021·Circulation Journal : Official Journal of the Japanese Circulation Society·Jung-Kyu HanHyo-Soo Kim

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Datasets Mentioned

BETA
SRP135657
GSE70872
GSE78938
SRP136063

Methods Mentioned

BETA
PCR
transgenic
RNA-seq
co-immunoprecipitation
dissection

Software Mentioned

GraphPad Prism
Cytoscape
EnrichmentMap
Patch Master
Excel
Ethovision
HOMER ( Optimization of Motif EnRichment
Tophat
R
BiQ Analyzer

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