Generation of pure GABAergic neurons by transcription factor programming

Nature Methods
Nan YangMarius Wernig

Abstract

Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human PSCs. Here, we show that transient expression of the transcription factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic neurons from human PSCs with a high degree of synaptic maturation. These AD-induced neuronal (iN) cells represent largely nonoverlapping populations of GABAergic neurons that express various subtype-specific markers. We further used AD-iN cells to establish that human collybistin, the loss of gene function of which causes severe encephalopathy, is required for inhibitory synaptic function. The generation of defined populations of functionally mature human GABAergic neurons represents an important step toward enabling the study of diseases affecting inhibitory synaptic transmission.

References

Dec 22, 1998·Histochemistry and Cell Biology·B FrankeJ Engele
Jun 25, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kirsten HarveyRobert J Harvey
Jun 24, 2008·Nature Reviews. Neuroscience·UNKNOWN Petilla Interneuron Nomenclature GroupRafael Yuste
Nov 26, 2008·Molecular and Cellular Neurosciences·Gregory B PotterJohn L R Rubenstein
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Jan 29, 2010·Nature·Thomas VierbuchenMarius Wernig
Apr 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yue XuSheng Ding
Aug 17, 2010·Nature Methods·Joshua Z LevinAviv Regev
Dec 15, 2010·Developmental Neurobiology·Nada ZecevicIgor Jakovcevski
May 28, 2011·Nature·Zhiping P PangMarius Wernig
Jun 1, 2011·American Journal of Medical Genetics. Part a·Gaetan LescaDamien Sanlaville
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ulrich PfistererMalin Parmar
Jul 15, 2011·Nature·Andrew S YooGerald R Crabtree
Aug 20, 2011·Cell Stem Cell·Esther Y SonKevin Eggan
Nov 15, 2011·Nature Biotechnology·Piero DalerbaStephen R Quake
Sep 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Soham ChandaThomas C Südhof
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Simone MayerTheofilos Papadopoulos
Sep 26, 2014·Stem Cell Reports·Soham ChandaMarius Wernig
Nov 28, 2014·Science Translational Medicine·Vittorio SebastianoAnthony E Oro
Jun 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Spyros DarmanisStephen R Quake

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Citations

Nov 2, 2017·Scientific Reports·Simon D KlapperVolker Busskamp
Sep 2, 2017·FEBS Letters·Miguel Turrero García, Corey C Harwell
Dec 6, 2018·International Journal of Molecular Sciences·Anke HoffmannDietmar Spengler
Aug 18, 2018·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Joseph A FantuzzoZhiping P Pang
Jan 31, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Congyi LuJen Q Pan
Mar 7, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Hang-Soo ParkSunghoi Hong
May 10, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·John D Blair, Helen S Bateup
Mar 24, 2020·Nature Genetics·Michael B FernandoKristen J Brennand
Mar 4, 2020·Stem Cells and Development·Alejandro De Los Angeles, Elizabeth M Tunbridge
Apr 18, 2020·Molecular Autism·Aaron Gordon, Daniel H Geschwind
Sep 25, 2019·Nature Genetics·Nadine SchrodeKristen J Brennand
Jun 4, 2020·Molecular Autism·Danijela DrakulicAdrian J Harwood
Jul 13, 2019·Annual Review of Neuroscience·Gord Fishell, Adam Kepecs
Jan 6, 2018·Npj Regenerative Medicine·Sofia Grade, Magdalena Götz
Apr 27, 2019·Frontiers in Cellular Neuroscience·Dario PacittiBridget E Bax
Jun 23, 2019·Scientific Reports·BanuPriya SridharanTimothy P Spicer
Dec 1, 2019·Nature Genetics·Erin FlahertyKristen J Brennand
Apr 16, 2020·Molecular Autism·Ralda Nehme, Lindy E Barrett
Jun 9, 2020·Frontiers in Cellular Neuroscience·Lea J FlitschOliver Brüstle
Jul 17, 2020·International Journal of Molecular Sciences·Tetsuya YoshizumiHiroshi Kanno
Jul 8, 2018·Journal of Inherited Metabolic Disease·Sabine Jung-Klawitter, Thomas Opladen
Sep 27, 2018·Nature Neuroscience·Hongjun FuKaren E Duff
Jun 27, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Wei Niu, Jack M Parent
Jan 17, 2020·International Journal of Molecular Sciences·Bruno SterliniAnna Corradi
Sep 27, 2018·Epilepsy Currents·Dina Simkin, Evangelos Kiskinis
Nov 30, 2019·Nature Reviews. Neuroscience·Rik van der KantRik Ossenkoppele
Apr 12, 2019·Frontiers in Neuroscience·Gaia ColasanteVania Broccoli
Jun 25, 2019·Frontiers in Cell and Developmental Biology·Ning-Xin MaGong Chen
Jul 9, 2020·APL Bioengineering·Aditya Kumar, Prashant Mali
Jun 21, 2020·International Journal of Molecular Sciences·Roxanne Hsiang-Chi LiouRaymond Ching-Bong Wong

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