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Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise

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Abstract

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

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References

  1. Pesaresi M, Sebastian-Perez R, Cosma MP. Dedifferentiation, transdifferentiation and cell fusion: In vivo reprogramming strategies for regenerative medicine. FEBS J 2019, 286: 1074–1093.

    Article  CAS  PubMed  Google Scholar 

  2. Lenkowski JR, Raymond PA. Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish. Prog Retin Eye Res 2014, 40: 94–123.

    Article  PubMed  Google Scholar 

  3. Fischer AJ, Reh TA. Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci 2001, 4: 247–252.

    Article  CAS  PubMed  Google Scholar 

  4. Karl MO, Reh TA. Studying the generation of regenerated retinal neuron from Müller glia in the mouse eye. Methods Mol Biol, 2012, 884: 213–227.

  5. Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders–how to make it work. Nat Med 2004, 10: S42–S50.

    Article  PubMed  CAS  Google Scholar 

  6. Gonçalves JT, Schafer ST, Gage FH. Adult neurogenesis in the hippocampus: From stem cells to behavior. Cell 2016, 167: 897–914.

    Article  PubMed  CAS  Google Scholar 

  7. Goodman T, Hajihosseini MK. Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front Neurosci 2015, 9: 387.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lim DA, Alvarez-Buylla A. The adult ventricular–subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb Perspect Biol 2016, 8: a018820.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Ming GL, Song H. Adult neurogenesis in the mammalian brain: Significant answers and significant questions. Neuron 2011, 70: 687–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gage FH. Adult neurogenesis in mammals. Science 2019, 364: 827–828.

    Article  CAS  PubMed  Google Scholar 

  11. Goldman SA. Directed mobilization of endogenous neural progenitor cells: The intersection of stem cell biology and gene therapy. Curr Opin Mol Ther 2004, 6: 466–472.

    PubMed  Google Scholar 

  12. Steinbeck JA, Studer L. Moving stem cells to the clinic: Potential and limitations for brain repair. Neuron 2015, 86: 187–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goldman SA. Stem and progenitor cell-based therapy of the central nervous system: Hopes, hype, and wishful thinking. Cell Stem Cell 2016, 18: 174–188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang L, Yin JC, Yeh H, Ma NX, Lee G, Chen XA, et al. Small molecules efficiently reprogram human astroglial cells into functional neurons. Cell Stem Cell 2015, 17: 735–747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 2008, 455: 627–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Barker RA, Götz M, Parmar M. New approaches for brain repair-from rescue to reprogramming. Nature 2018, 557: 329–334.

    Article  CAS  PubMed  Google Scholar 

  17. Torper O, Götz M. Brain repair from intrinsic cell sources: Turning reactive glia into neurons. Prog Brain Res 2017, 230: 69–97.

    Article  PubMed  Google Scholar 

  18. Wang LL, Zhang CL. Engineering new neurons: In vivo reprogramming in mammalian brain and spinal cord. Cell Tissue Res 2018, 371: 201–212.

    Article  CAS  PubMed  Google Scholar 

  19. Lei WL, Li W, Ge LJ, Chen G. Non-engineered and engineered adult neurogenesis in mammalian brains. Front Neurosci 2019, 13: 131.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009, 32: 638–647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, et al. Glial cells generate neurons: The role of the transcription factor Pax6. Nat Neurosci 2002, 5: 308–315.

    Article  CAS  PubMed  Google Scholar 

  22. Buffo A, Vosko MR, Ertürk D, Hamann GF, Jucker M, Rowitch D, et al. Expression pattern of the transcription factor Olig2 in response to brain injuries: Implications for neuronal repair. Proc Natl Acad Sci U S A 2005, 102: 18183–18188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Berninger B, Costa MR, Koch U, Schroeder T, Sutor B, Grothe B, et al. Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J Neurosci 2007, 27: 8654–8664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Heinrich C, Blum R, Gascón S, Masserdotti G, Tripathi P, Sánchez R, et al. Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biol 2010, 8: e1000373.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Addis RC, Hsu FC, Wright RL, Dichter MA, Coulter DA, Gearhart JD. Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector. PLoS One 2011, 6: e28719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 2010, 463: 1035–1041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Torper O, Pfisterer U, Wolf DA, Pereira M, Lau S, Jakobsson J, et al. Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci U S A 2013, 110: 7038–7043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Niu W, Zang T, Smith DK, Vue TY, Zou Y, Bachoo R, et al. SOX2 reprograms resident astrocytes into neural progenitors in the adult brain. Stem Cell Reports 2015, 4: 780–794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Niu W, Zang T, Zou Y, Fang S, Smith DK, Bachoo R, et al. In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat Cell Biol 2013, 15: 1164–1175.

    Article  CAS  PubMed  Google Scholar 

  30. Su Z, Niu W, Liu ML, Zou Y, Zhang CL. In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun 2014, 5: 3338.

    Article  PubMed  CAS  Google Scholar 

  31. Heinrich C, Bergami M, Gascón S, Lepier A, Viganò F, Dimou L, et al. Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Reports 2014, 3: 1000–1014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tai WJ, Wu W, Wang LL, Ni HQ, Chen CH, Yang JJ, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Grande A, Sumiyoshi K, López-Juárez A, Howard J, Sakthivel B, Aronow B, et al. Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nat Commun 2013, 4: 2373.

    Article  PubMed  Google Scholar 

  34. Gascón S, Murenu E, Masserdotti G, Ortega F, Russo GL, Petrik D, et al. Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming. Cell Stem Cell 2016, 18: 396–409.

    Article  PubMed  CAS  Google Scholar 

  35. Mattugini N, Bocchi R, Scheuss V, Russo GL, Torper O, Lao CL, et al. Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex. Neuron 2019, 103: 1086-1095.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen YC, Ma NX, Pei ZF, Wu Z, Do-Monte FH, Keefe S, et al. A NeuroD1 AAV-based gene therapy for functional brain repair after ischemic injury through in vivo astrocyte-to-neuron conversion. Mol Ther 2020, 28: 217–234.

    Article  CAS  PubMed  Google Scholar 

  37. Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G. 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.

    Article  CAS  PubMed  Google Scholar 

  38. Wu Z, Parry M, Hou XY, Liu MH, Wang H, Cain R, et al. Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington’s disease. Nat Commun 2020, 11: 1105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Torper O, Ottosson DR, Pereira M, Lau S, Cardoso T, Grealish S, et al. In vivo reprogramming of striatal NG2 glia into functional neurons that integrate into local host circuitry. Cell Rep 2015, 12: 474–481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pereira M, Birtele M, Shrigley S, Benitez JA, Hedlund E, Parmar M, et al. Direct reprogramming of resident NG2 glia into neurons with properties of fast-spiking parvalbumin-containing interneurons. Stem Cell Reports 2017, 9: 742–751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rivetti di Val Cervo P, Romanov RA, Spigolon G, Masini D, Martín-Montañez E, Toledo EM, 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.

  42. Liu YG, Miao QL, Yuan JC, Han SE, Zhang PP, Li SL, et al. Ascl1 converts dorsal midbrain astrocytes into functional neurons in vivo. J Neurosci 2015, 35: 9336–9355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ueki Y, Wilken MS, Cox KE, Chipman L, Jorstad N, Sternhagen K, et al. Transgenic expression of the proneural transcription factor Ascl1 in Müller glia stimulates retinal regeneration in young mice. Proc Natl Acad Sci U S A 2015, 112: 13717–13722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Li H, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 2013, 152: 82–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Qian H, Kang X, Hu J, Zhang D, Liang Z, Meng F, et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 2020, 582: 550–556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Weinberg MS, Criswell HE, Powell SK, Bhatt AP, McCown TJ. Viral vector reprogramming of adult resident striatal oligodendrocytes into functional neurons. Mol Ther 2017, 25: 928–934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhou H, Su J, Hu X, Zhou C, Li H, Chen Z, et al. Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice. Cell 2020, 181: 590–603.

    Article  CAS  PubMed  Google Scholar 

  48. Yin JC, Zhang L, Ma NX, Wang Y, Lee G, Hou XY, et al. Chemical conversion of human fetal astrocytes into neurons through modulation of multiple signaling pathways. Stem Cell Rep 2019, 12: 488–501.

    Article  CAS  Google Scholar 

  49. Ma Y, Xie H, Du X, Wang L, Jin X, Zhang Q, et al. In vivo chemical reprogramming of astrocytes into neurons. Cell Discov 2021, 7: 12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Aravantinou-Fatorou K, Ortega F, Chroni-Tzartou D, Antoniou N, Poulopoulou C, Politis PK, et al. CEND1 and NEUROGENIN2 reprogram mouse astrocytes and embryonic fibroblasts to induced neural precursors and differentiated neurons. Stem Cell Reports 2015, 5: 405–418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rao Z, Wang R, Li S, Shi Y, Mo L, Han S, et al. Molecular mechanisms underlying Ascl1-mediated astrocyte-to-neuron conversion. Stem Cell Reports 2021, 16: 534–547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ma NX, Yin JC, Chen G. Transcriptome analysis of small molecule-mediated astrocyte-to-neuron reprogramming. Front Cell Dev Biol 2019, 7: 82.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Raposo AASF, Vasconcelos FF, Drechsel D, Marie C, Johnston C, Dolle D, et al. Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis. Cell Rep 2015, 10: 1544–1556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zaret KS, Carroll JS. Pioneer transcription factors: Establishing competence for gene expression. Genes Dev 2011, 25: 2227–2241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pollak J, Wilken MS, Ueki Y, Cox KE, Sullivan JM, Taylor RJ, et al. ASCL1 reprograms mouse Müller glia into neurogenic retinal progenitors. Development 2013, 140: 2619–2631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Masserdotti G, Gillotin S, Sutor B, Drechsel D, Irmler M, Jørgensen HF, et al. Transcriptional mechanisms of proneural factors and REST in regulating neuronal reprogramming of astrocytes. Cell Stem Cell 2015, 17: 74–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Xue Y, Qian H, Hu J, Zhou B, Zhou Y, Hu X, et al. Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells. Nat Neurosci 2016, 19: 807–815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Janowska J, Gargas J, Ziemka-Nalecz M, Zalewska T, Buzanska L, Sypecka J. Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp Neurol 2019, 319: 112813.

    Article  CAS  PubMed  Google Scholar 

  59. Yavarpour-Bali H, Ghasemi-Kasman M, Shojaei A. Direct reprogramming of terminally differentiated cells into neurons: A novel and promising strategy for Alzheimer’s disease treatment. Prog Neuropsychopharmacol Biol Psychiatry 2020, 98: 109820.

    Article  CAS  PubMed  Google Scholar 

  60. Matsuda T, Irie T, Katsurabayashi S, Hayashi Y, Nagai T, Hamazaki N, et al. Pioneer factor NeuroD1 rearranges transcriptional and epigenetic profiles to execute microglia-neuron conversion. Neuron 2019, 101: 472–485.

    Article  CAS  PubMed  Google Scholar 

  61. Jorstad NL, Wilken MS, Grimes WN, Wohl SG, VandenBosch LS, Yoshimatsu T, et al. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 2017, 548: 103–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Karimi-Abdolrezaee S, Billakanti R. Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol 2012, 46: 251–264.

    Article  CAS  PubMed  Google Scholar 

  63. Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, et al. Dual functions of microglia in ischemic stroke. Neurosci Bull 2019, 35: 921–933.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Liu MH, Li W, Zheng JJ, Xu YG, He Q, Chen G. Differential neuronal reprogramming induced by NeuroD1 from astrocytes in grey matter versus white matter. Neural Regen Res 2020, 15: 342–351.

    Article  PubMed  Google Scholar 

  65. Bayraktar OA, Bartels T, Holmqvist S, Kleshchevnikov V, Martirosyan A, Polioudakis D, et al. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat Neurosci 2020, 23: 500–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Boisvert MM, Erikson GA, Shokhirev MN, Allen NJ. The aging astrocyte transcriptome from multiple regions of the mouse brain. Cell Rep 2018, 22: 269–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Russo I, Barlati S, Bosetti F. Effects of neuroinflammation on the regenerative capacity of brain stem cells. J Neurochem 2011, 116: 947–956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wan J, Zhao XF, Vojtek A, Goldman D. Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration. Cell Rep 2014, 9: 285–297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zamboni M, Llorens-Bobadilla E, Magnusson JP, Frisén J. A widespread neurogenic potential of neocortical astrocytes is induced by injury. Cell Stem Cell 2020, 27: 605–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Grade S, Götz M. Neuronal replacement therapy: Previous achievements and challenges ahead. NPJ Regen Med 2017, 2: 29.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Vignoles R, Lentini C, d’Orange M, Heinrich C. Direct lineage reprogramming for brain repair: Breakthroughs and challenges. Trends Mol Med 2019, 25: 897–914.

    Article  CAS  PubMed  Google Scholar 

  72. Chen Y, Xiong M, Dong Y, Haberman A, Cao J, Liu H, et al. Chemical control of grafted human PSC-derived neurons in a mouse model of Parkinson’s disease. Cell Stem Cell 2016, 18: 817–826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Steinbeck JA, Choi SJ, Mrejeru A, Ganat Y, Deisseroth K, Sulzer D, et al. Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model. Nat Biotechnol 2015, 33: 204–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Fang L, El Wazan L, Tan C, Nguyen T, Hung SSC, Hewitt AW, et al. Potentials of cellular reprogramming as a novel strategy for neuroregeneration. Front Cell Neurosci 2018, 12: 460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Gascón S, Masserdotti G, Russo GL, Götz M. Direct neuronal reprogramming: achievements, hurdles, and new roads to success. Cell Stem Cell 2017, 21: 18–34.

    Article  PubMed  CAS  Google Scholar 

  76. Xiong WJ, Wu DM, Xue YL, Wang SK, Chung MJ, Ji XK, et al. AAV cis-regulatory sequences are correlated with ocular toxicity. Proc Natl Acad Sci U S A 2019, 116: 5785–5794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Khabou H, Cordeau C, Pacot L, Fisson S, Dalkara D. Dosage thresholds and influence of transgene cassette in adeno-associated virus-related toxicity. Hum Gene Ther 2018, 29: 1235–1241.

    Article  CAS  PubMed  Google Scholar 

  78. Xiang Z, Xu L, Liu M, Wang Q, Li W, Lei W, et al. Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex. Neural Regen Res 2021, 16: 750–756.

    Article  PubMed  Google Scholar 

  79. Qian C, Dong B, Wang XY, Zhou FQ. In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system. FEBS J 2020, https://doi.org/10.1111/febs.15681.

    Article  PubMed  Google Scholar 

  80. de Melo Guimarães RP, Landeira BS, Coelho DM, Golbert DCF, Silveira MS, Linden R, et al. Evidence of Müller glia conversion into retina ganglion cells using neurogenin2. Front Cell Neurosci 2018, 12: 410.

    Article  CAS  Google Scholar 

  81. Li S, Shi Y, Yao X, Wang X, Shen L, Rao Z, et al. Conversion of astrocytes and fibroblasts into functional noradrenergic neurons. Cell Rep 2019, 28: 682-697.e7.

    Article  CAS  PubMed  Google Scholar 

  82. Chakraborty S, Ji H, Kabadi AM, Gersbach CA, Christoforou N, Leong KW. A CRISPR/Cas9-based system for reprogramming cell lineage specification. Stem Cell Reports 2014, 3: 940–947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Liu Y, Yu C, Daley TP, Wang F, Cao WS, Bhate S, et al. CRISPR activation screens systematically identify factors that drive neuronal fate and reprogramming. Cell Stem Cell 2018, 23: 758–771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Giacomoni J, Bruzelius A, Stamouli CA, Rylander Ottosson D. Direct conversion of human stem cell-derived glial progenitor cells into GABAergic interneurons. Cells 2020, 9: 2451.

    Article  CAS  PubMed Central  Google Scholar 

  85. Nolbrant S, Giacomoni J, Hoban DB, Bruzelius A, Birtele M, Chandler-Militello D, et al. Direct reprogramming of human fetal- and stem cell-derived glial progenitor cells into midbrain dopaminergic neurons. Stem Cell Reports 2020, 15: 869–882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This review was supported by grants from the National Natural Science Foundation of China (32071025), the Beijing Municipal Science & Technology Commission (Z181100001518001), and the Interdisciplinary Research Fund of Beijing Normal University, and the Science and Technology Program of Guangxi (AD21075052), the National Natural Science Foundation of China (31871037 and 32070976), and the Guangxi First-class Discipline Project for Basic Medicine Sciences (GXFCDP-BMS-2018).

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  1. State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China

    Fengchao Wang & Xiaohui Zhang

  2. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, and Guangxi Key Laboratory of Regenerative Medicine, Center for Translational Medicine, Guangxi Medical University, Nanning, 530021, China

    Leping Cheng

  3. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China

    Leping Cheng

  4. Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, Guangxi Medical University, Nanning, 530021, China

    Leping Cheng

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  1. Fengchao Wang
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Wang, F., Cheng, L. & Zhang, X. Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise. Neurosci. Bull. 37, 1625–1636 (2021). https://doi.org/10.1007/s12264-021-00751-3

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