Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules

Stem Cells International
Yan-Chuang HanXin-Fu Zhou

Abstract

Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical...Continue Reading

References

Sep 5, 2001·Nature Cell Biology·J G TomaF D Miller
Dec 7, 2002·Nature Neuroscience·Karen LaiDavid V Schaffer
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Gangning LiangPeter A Jones
Jun 26, 2004·Molecular and Cellular Biology·Hironobu KimuraTakashi Tada
Oct 28, 2005·Nature·Dieter-Chichung LieFred H Gage
Aug 31, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Steven A Goldman, Martha S Windrem
Dec 5, 2006·Methods in Enzymology·Rodney L Rietze, Brent A Reynolds
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tomoyuki MiyabayashiMichael Kahn
Jan 29, 2008·Current Stem Cell Research & Therapy·Jin Han, Kuldip S Sidhu
May 24, 2008·Nature·Qi-Long YingAustin Smith
Oct 14, 2008·Nature Biotechnology·Danwei HuangfuDouglas A Melton
Jan 27, 2009·Development·Konrad Hochedlinger, Kathrin Plath
Apr 7, 2009·Cell·Shinya Yamanaka
May 12, 2009·Cell Stem Cell·Jacob HannaRudolf Jaenisch
Jul 11, 2009·Nature Biotechnology·Kyoko MiuraShinya Yamanaka
Dec 29, 2009·Cell Stem Cell·Miguel Angel EstebanDuanqing Pei
Jul 29, 2010·Journal of Cellular Biochemistry·Chui-Yee FongAriff Bongso
Apr 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Janghwan KimSheng Ding
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ernesto LujanMarius Wernig
Mar 27, 2012·Cell Stem Cell·Dong Wook HanHans R Schöler
Mar 27, 2012·Cell Stem Cell·Marc ThierFrank Edenhofer
Dec 24, 2014·Cell Reports·William B Hamilton, Joshua M Brickman
Apr 30, 2015·Stem Cells International·Tongxiang Lin, Shouhai Wu

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Citations

Nov 1, 2016·Stem Cells and Development·Ankshita PrasadAngelo H All
Jan 23, 2017·Redox Biology·Zhimin XuJian Feng
Jan 19, 2018·Stem Cells and Development·Donghui LiuHong Liao
May 22, 2019·Frontiers in Neurology·Maria R GanchevaSimon A Koblar
Feb 19, 2020·Cell Biology International·Divya DesaiPrasad Pethe
May 10, 2018·Bioscience Reports·Yukimasa TakedaPing Dai
Nov 15, 2019·Scientific Reports·Guosheng XuYin-Xiong Li
Jul 13, 2017·Cellular and Molecular Life Sciences : CMLS·Hua QinXiaobing Fu
Apr 14, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kenichi Horisawa, Atsushi Suzuki
Nov 5, 2020·Stem Cells International·Zhao-Di YuanYan-Chuang Han
Sep 25, 2017·Methods : a Companion to Methods in Enzymology·Ebrahim ShahbaziHossein Baharvand
Jun 23, 2020·Current Stem Cell Research & Therapy·Jun ZengMin Hu

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Methods Mentioned

BETA
Profiler
PCR
FACS
reverse transcription PCR
acetylation

Software Mentioned

Patch Master
Expo MultiComp

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