Grade S Gotz M Neuronal replacement therapy: previous achievements and challenges ahead NPJ Regen. Med. 2017 2 29 29302363 5677983 10.1038/s41536-017-0033-0
Barker RA Gotz M Parmar M New approaches for brain repair-from rescue to reprogramming Nature 2018 557 329 334 1:CAS:528:DC%2BC1cXpvVSgtbo%3D 29769670 10.1038/s41586-018-0087-1
Bocchi R Masserdotti G Götz M Direct neuronal reprogramming: fast forward from new concepts toward therapeutic approaches Neuron 2021 10.1016/j.neuron.2021.11.023 34921778
Vasan L Park E David LA Fleming T Schuurmans C Direct neuronal reprogramming: bridging the gap between basic science and clinical application Front Cell Dev. Biol. 2021 9 34291049 8287587 10.3389/fcell.2021.681087 681087
Pushchina, E. V., Kapustyanov, I. A. Kluka, G. G. Adult neurogenesis of teleost fish determines high neuronal plasticity and regeneration. Int. J. Mol. Sci. https://doi.org/10.3390/ijms25073658 (2024).
Qian H et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons Nature 2020 582 550 556 1:CAS:528:DC%2BB3cXht1ClsrvP 32581380 7521455 10.1038/s41586-020-2388-4
Irie, T. Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke. bioRxiv https://doi.org/10.1101/2021.09.26.461831 (2021).
Livingston JM et al. Ectopic expression of Neurod1 is sufficient for functional recovery following a sensory–motor cortical stroke Biomedicines 2024 12 663 1:CAS:528:DC%2BB2cXnsFGlsrc%3D 38540276 10968474 10.3390/biomedicines12030663
Lentini C et al. Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy Cell Stem Cell 2021 10.1016/j.stem.2021.09.002 34592167 8657801
Zhang L et al. Development of neuroregenerative gene therapy to reverse glial scar tissue back to neuron-enriched tissue Front Cell Neurosci. 2020 14 1:CAS:528:DC%2BB3MXptVejs7k%3D 33250718 7674596 10.3389/fncel.2020.594170 594170
Tai W et al. In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury Cell Stem Cell 2021 28 923 937 e924 1:CAS:528:DC%2BB3MXmtVSmt7g%3D 33675690 8106641 10.1016/j.stem.2021.02.009
Rivetti di Val Cervo P et al. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson’s disease model Nat. Biotechnol. 2017 35 444 452 28398344 10.1038/nbt.3835
Zhou H et al. Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice Cell 2020 181 590 603.e516 1:CAS:528:DC%2BB3cXmvFGms7c%3D 32272060 10.1016/j.cell.2020.03.024
Wang LL et al. Revisiting astrocyte to neuron conversion with lineage tracing in vivo Cell 2021 184 5465 5481 e5416 1:CAS:528:DC%2BB3MXitFWgtLbL 34582787 8526404 10.1016/j.cell.2021.09.005
Rao Y et al. NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming Neuron 2021 109 4094 4108.e4095 1:CAS:528:DC%2BB3MXis1OntLrM 34875233 10.1016/j.neuron.2021.11.008
Wang D Tai PWL Gao G Adeno-associated virus vector as a platform for gene therapy delivery Nat. Rev. Drug Discov. 2019 18 358 378 1:CAS:528:DC%2BC1MXmtFKitL0%3D 30710128 6927556 10.1038/s41573-019-0012-9
Xie Y Zhou J Wang LL Zhang CL Chen B New AAV tools fail to detect Neurod1-mediated neuronal conversion of Müller glia and astrocytes in vivo EBioMedicine 2023 90 1:CAS:528:DC%2BB3sXls1ykur4%3D 36947961 10033723 10.1016/j.ebiom.2023.104531 104531
Le N Appel H Pannullo N Hoang T Blackshaw S Ectopic insert-dependent neuronal expression of GFAP promoter-driven AAV constructs in adult mouse retina Front Cell Dev. Biol. 2022 10 36200040 9527291 10.3389/fcell.2022.914386 914386
Puglisi, M. et al. Comparing viral vectors and fate mapping approaches for astrocyte-to-neuron reprogramming in the injured mouse cerebral cortex. Cells https://doi.org/10.3390/cells13171408 (2024).
Guo Z et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model Cell Stem Cell 2014 14 188 202 1:CAS:528:DC%2BC3sXhvFyktrzJ 24360883 10.1016/j.stem.2013.12.001
Enbar T et al. Regionally distinct GFAP promoter expression plays a role in off-target neuron expression following AAV5 transduction Sci. Rep. 2024 14 1:CAS:528:DC%2BB2MXnvVOruw%3D%3D 39738170 11685643 10.1038/s41598-024-79124-5 31583
Casarosa S Fode C Guillemot F Mash1 regulates neurogenesis in the ventral telencephalon Development 1999 126 525 534 1:CAS:528:DyaK1MXhsVSlu7g%3D 9876181 10.1242/dev.126.3.525
Horton S Meredith A Richardson JA Johnson JE Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1 Mol. Cell Neurosci. 1999 14 355 369 1:CAS:528:DyaK1MXmvFGnsb8%3D 10588390 10.1006/mcne.1999.0791
Parras CM et al. Mash1 specifies neurons and oligodendrocytes in the postnatal brain EMBO J. 2004 23 4495 4505 1:CAS:528:DC%2BD2cXpsFahur4%3D 15496983 526464 10.1038/sj.emboj.7600447
Parras CM et al. The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes J. Neurosci. 2007 27 4233 4242 1:CAS:528:DC%2BD2sXkvFCjsbw%3D 17442807 6672315 10.1523/JNEUROSCI.0126-07.2007
Han S et al. Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding Neuron 2021 109 2847 2863.e2811 1:CAS:528:DC%2BB3MXhvVSku77P 34407390 12080610 10.1016/j.neuron.2021.07.007
Heinrich C Gotz M Berninger B Reprogramming of postnatal astroglia of the mouse neocortex into functional, synapse-forming neurons Methods Mol. Biol. 2012 814 485 498 1:CAS:528:DC%2BC38XhslWisrbL 22144327 10.1007/978-1-61779-452-0_32
Li S et al. RAS/ERK signaling controls proneural genetic programs in cortical development and gliomagenesis J. Neurosci. 2014 34 2169 2190 24501358 6608536 10.1523/JNEUROSCI.4077-13.2014
Li S et al. GSK3 temporally regulates neurogenin 2 proneural activity in the neocortex J. Neurosci. 2012 32 7791 7805 1:CAS:528:DC%2BC38XovFSmu7w%3D 22674256 6620952 10.1523/JNEUROSCI.1309-12.2012
Hand R et al. Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex Neuron 2005 48 45 62 1:CAS:528:DC%2BD2MXhtFelt7rI 16202708 10.1016/j.neuron.2005.08.032
Ge W et al. Coupling of cell migration with neurogenesis by proneural bHLH factors Proc. Natl Acad. Sci. USA 2006 103 1319 1324 1:CAS:528:DC%2BD28Xhs1Ggu74%3D 16432194 1345712 10.1073/pnas.0510419103
Sun Y et al. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms Cell 2001 104 365 376 1:CAS:528:DC%2BD3MXis1ejsLk%3D 11239394 10.1016/S0092-8674(01)00224-0
Ali F et al. Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell cycling with differentiation during neurogenesis Development 2011 138 4267 4277 1:CAS:528:DC%2BC3MXhsVOgsrrL 21852393 3171226 10.1242/dev.067900
Ali FR et al. Dephosphorylation of the proneural transcription factor ASCL1 re-engages a latent post-mitotic differentiation program in neuroblastoma Mol. Cancer Res. 2020 18 1759 1766 1:CAS:528:DC%2BB3MXjs1aktg%3D%3D 33046535 7614603 10.1158/1541-7786.MCR-20-0693
Azzarelli R Hardwick LJ Philpott A Emergence of neuronal diversity from patterning of telencephalic progenitors Wiley Interdiscip. Rev. Dev. Biol. 2015 4 197 214 25619507 10.1002/wdev.174
Azzarelli R et al. ASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation Sci. Rep. 2022 12 1:CAS:528:DC%2BB38XjsVGku7o%3D 35149717 8837758 10.1038/s41598-022-06248-x 2341
Hindley C et al. Post-translational modification of Ngn2 differentially affects transcription of distinct targets to regulate the balance between progenitor maintenance and differentiation Development 2012 139 1718 1723 1:CAS:528:DC%2BC38XpsFWgsrg%3D 22491944 3328174 10.1242/dev.077552
Lende-Dorn BA Atkinson JC Bae Y Galloway KE Chemogenetic tuning reveals optimal MAPK signaling for cell-fate programming Cell Rep. 2025 44 116226 1:CAS:528:DC%2BB2MXitF2is7zN 40913769 12571515 10.1016/j.celrep.2025.116226
Ghazale H et al. Ascl1 phospho-site mutations enhance neuronal conversion of adult cortical astrocytes in vivo Front Neurosci. 2022 16 917071 36061596 9434350 10.3389/fnins.2022.917071
Marichal N et al. Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site-deficient Ascl1 Sci. Adv. 2024 10 eadl5935 39454007 11506222 10.1126/sciadv.adl5935
Pereira A et al. Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1 Nat. Neurosci. 2024 27 1260 1273 1:CAS:528:DC%2BB2cXhsVOnt7vK 38956165 11239498 10.1038/s41593-024-01677-5
Lee SW Oh YM Lu YL Kim WK Yoo AS MicroRNAs overcome cell fate barrier by reducing EZH2-controlled REST stability during neuronal conversion of human adult fibroblasts Dev. Cell 2018 46 73 84.e77 1:CAS:528:DC%2BC1cXht1yis73K 29974865 6082428 10.1016/j.devcel.2018.06.007
Pestana, F., Edwards-Faret, G., Belgard, T. G., Martirosyan, A. & Holt, M. G. No longer underappreciated: the emerging concept of astrocyte heterogeneity in neuroscience. Brain Sci. https://doi.org/10.3390/brainsci10030168 (2020).
Taschenberger G Tereshchenko J Kügler S A microRNA124 target sequence restores astrocyte specificity of gfaABC1D-driven transgene expression in AAV-mediated gene transfer Mol. Ther. Nucleic Acids 2017 8 13 25 1:CAS:528:DC%2BC2sXhsFSktLrI 28918015 5476465 10.1016/j.omtn.2017.03.009
Zhang X et al. CellMarker: a manually curated resource of cell markers in human and mouse Nucleic Acids Res. 2019 47 D721 D728 1:CAS:528:DC%2BC1MXhs1Clu77E 30289549 10.1093/nar/gky900
Ciesielska A et al. Cerebral infusion of AAV9 vector-encoding non-self proteins can elicit cell-mediated immune responses Mol. Ther. 2013 21 158 166 1:CAS:528:DC%2BC38Xht1KrsrvE 22929660 10.1038/mt.2012.167
Miller SA et al. LSD1 and aberrant DNA methylation mediate persistence of enteroendocrine progenitors that support BRAF-mutant colorectal cancer Cancer Res. 2021 81 3791 3805 1:CAS:528:DC%2BB3MXhvFeks73I 34035083 8513805 10.1158/0008-5472.CAN-20-3562
Hardwick LJ Ali FR Azzarelli R Philpott A Cell cycle regulation of proliferation versus differentiation in the central nervous system Cell Tissue Res. 2015 359 187 200 1:CAS:528:DC%2BC2cXosFCmtbo%3D 24859217 10.1007/s00441-014-1895-8
Calegari F Haubensak W Haffner C Huttner WB Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development J. Neurosci. 2005 25 6533 6538 1:CAS:528:DC%2BD2MXmslCltL0%3D 16014714 6725437 10.1523/JNEUROSCI.0778-05.2005
Wang NB et al. Proliferation history and transcription factor levels drive direct conversion to motor neurons Cell Syst. 2025 16 101205 1:CAS:528:DC%2BB2MXmtFaltro%3D 40086434 10.1016/j.cels.2025.101205
Lie DC et al. Wnt signalling regulates adult hippocampal neurogenesis Nature 2005 437 1370 1375 1:CAS:528:DC%2BD2MXhtFCrur3M 16251967 10.1038/nature04108
Zhang L Yang X Yang S Zhang J The Wnt /β-catenin signaling pathway in the adult neurogenesis Eur. J. Neurosci. 2011 33 1 8 21073552 10.1111/j.1460-9568.2010.7483.x
Turner DA Adamson DC Neuronal-astrocyte metabolic interactions: understanding the transition into abnormal astrocytoma metabolism J. Neuropathol. Exp. Neurol. 2011 70 167 176 1:CAS:528:DC%2BC3MXit1eit78%3D 21293295 10.1097/NEN.0b013e31820e1152
Hartmann A Okawa S Zaffaroni G Del Sol A SeesawPred: a web application for predicting cell-fate determinants in cell differentiation Sci. Rep. 2018 8 30190516 6127256 10.1038/s41598-018-31688-9 13355
Kim DY Hwang I Muller FL Paik JH Functional regulation of FoxO1 in neural stem cell differentiation Cell Death Differ. 2015 22 2034 2045 1:CAS:528:DC%2BC2MXhs1ylurnO 26470727 4816100 10.1038/cdd.2015.123
Miron VE Microglia-driven regulation of oligodendrocyte lineage cells, myelination, and remyelination J. Leukoc. Biol. 2017 101 1103 1108 1:CAS:528:DC%2BC2sXhtFOqtL3P 28250011 10.1189/jlb.3RI1116-494R
Zhang, J., Yang, S.-G. & Zhou, F.-Q. Glycogen synthase kinase 3 signaling in neural regeneration in vivo. J. Mol. Cell Biol. https://doi.org/10.1093/jmcb/mjad075 (2023).
Zhang L et al. Small molecules efficiently reprogram human astroglial cells into functional neurons Cell Stem Cell 2015 17 735 747 1:CAS:528:DC%2BC2MXhs1OrsbbE 26481520 4675726 10.1016/j.stem.2015.09.012
Liu ML et al. Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons Nat. Commun. 2013 4 23873306 10.1038/ncomms3183 2183
Mseis-Jackson N et al. Dynamic regulation of NeuroD1 expression level by a novel viral construct during astrocyte-to-neuron reprogramming bioRxiv 2025 10.1101/2025.02.17.638625 40027739 11870611
Parras CM et al. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity Genes Dev. 2002 16 324 338 1:CAS:528:DC%2BD38XhtFWmu7k%3D 11825874 155336 10.1101/gad.940902
Kovach C et al. Neurog2 simultaneously activates and represses alternative gene expression programs in the developing neocortex Cereb. Cortex 2013 23 1884 1900 22735158 10.1093/cercor/bhs176
Chen G Shi Y Liu M Sun J circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma Cell Death Dis. 2018 9 175 29415990 5833724 10.1038/s41419-017-0204-3
Wang R et al. EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis Mol. Cancer 2018 17 1:CAS:528:DC%2BC1MXptlWhtL0%3D 30470262 6260852 10.1186/s12943-018-0911-0 166
Gu X et al. Molecular mechanisms involved in the regulation of neurodevelopment by miR-124 Mol. Neurobiol. 2023 60 3569 3583 1:CAS:528:DC%2BB3sXjvFClsLc%3D 36840845 10.1007/s12035-023-03271-5
Enokido T et al. Distinct microRNA signature and suppression of ZFP36L1 define ASCL1-positive lung adenocarcinoma Mol. Cancer Res. 2024 22 29 40 1:CAS:528:DC%2BB2cXntVansLw%3D 37801008 10.1158/1541-7786.MCR-23-0229
Papadimitriou E et al. A miR-124-mediated post-transcriptional mechanism controlling the cell fate switch of astrocytes to induced neurons Stem Cell Rep. 2023 18 915 935 1:CAS:528:DC%2BB3sXmtVals7k%3D 10.1016/j.stemcr.2023.02.009
Cates, K., Yuan, L., Yang, Y. & Yoo, A. S. Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs. Cell Rep. https://doi.org/10.1016/j.celrep.2024.115153 (2025).
Son G et al. miR-124 coordinates metabolic regulators acting at early stages of human neurogenesis Commun. Biol. 2024 7 1393 1:CAS:528:DC%2BB2cXitlelu7rO 39455851 11511827 10.1038/s42003-024-07089-2
Lee Y Messing A Su M Brenner M GFAP promoter elements required for region-specific and astrocyte-specific expression Glia 2008 56 481 493 18240313 10.1002/glia.20622
Bankhead P et al. QuPath: open source software for digital pathology image analysis Sci. Rep. 2017 7 29203879 5715110 10.1038/s41598-017-17204-5 16878