1932

Abstract

Cell replacement therapy represents a promising approach for treating neurodegenerative diseases. Contrary to the common addition strategy to generate new neurons from glia by overexpressing a lineage-specific transcription factor(s), a recent study introduced a subtraction strategy by depleting a single RNA-binding protein, Ptbp1, to convert astroglia to neurons not only in vitro but also in the brain. Given its simplicity, multiple groups have attempted to validate and extend this attractive approach but have met with difficulty in lineage tracing newly induced neurons from mature astrocytes, raising the possibility of neuronal leakage as an alternative explanation for apparent astrocyte-to-neuron conversion. This review focuses on the debate over this critical issue. Importantly, multiple lines of evidence suggest that Ptbp1 depletion can convert a selective subpopulation of glial cells into neurons and, via this and other mechanisms, reverse deficits in a Parkinson's disease model, emphasizing the importance of future efforts in exploring this therapeutic strategy.

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2023-07-10
2024-12-12
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Literature Cited

  1. Alber S, Di-Matteo P, Zdradzinski MD, Marvaldi L, Kawaguchi R et al. 2020. PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons. bioRxiv 2020.2010.2022.348631. https://doi.org/10.1101/2020.10.22.348631
  2. Álvarez-Aznar A, Martínez-Corral I, Daubel N, Betsholtz C, Makinen T, Gaengel K. 2020. Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreERT2 lines. Transgenic Res. 29:53–68
    [Google Scholar]
  3. Anthony TE, Klein C, Fishell G, Heintz N. 2004. Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41:881–90
    [Google Scholar]
  4. Aoki H, Hara A, Era T, Kunisada T, Yamada Y. 2012. Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis. Development 139:667–77
    [Google Scholar]
  5. Arnold P, Scholer A, Pachkov M, Balwierz PJ, Jorgensen H et al. 2013. Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting. Genome Res. 23:60–73
    [Google Scholar]
  6. Babic I, Sharma S, Black DL. 2009. A role for polypyrimidine tract binding protein in the establishment of focal adhesions. Mol. Cell. Biol. 29:5564–77
    [Google Scholar]
  7. Baker DJ, Petersen RC. 2018. Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives. J. Clin. Investig. 128:1208–16
    [Google Scholar]
  8. Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G. 2005. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121:645–57
    [Google Scholar]
  9. Barker RA, Gotz M, Parmar M. 2018. New approaches for brain repair—from rescue to reprogramming. Nature 557:329–34
    [Google Scholar]
  10. Ben Haim L, Rowitch DH 2017. Functional diversity of astrocytes in neural circuit regulation. Nat. Rev. Neurosci. 18:31–41
    [Google Scholar]
  11. Birch J, Gil J. 2020. Senescence and the SASP: many therapeutic avenues. Genes Dev. 34:1565–76
    [Google Scholar]
  12. Bocchi R, Masserdotti G, Gotz M. 2022. Direct neuronal reprogramming: fast forward from new concepts toward therapeutic approaches. Neuron 110:366–93
    [Google Scholar]
  13. Bohin N, Carlson EA, Samuelson LC. 2018. Genome toxicity and impaired stem cell function after conditional activation of CreERT2 in the intestine. Stem Cell Rep. 11:1337–46
    [Google Scholar]
  14. Borodinova AA, Balaban PM, Bezprozvanny IB, Salmina AB, Vlasova OL 2021. Genetic constructs for the control of astrocytes' activity. Cells 10:1600
    [Google Scholar]
  15. Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G et al. 2007. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21:1636–52
    [Google Scholar]
  16. Caldwell AB, Liu Q, Schroth GP, Galasko DR, Yuan SH et al. 2020. Dedifferentiation and neuronal repression define familial Alzheimer's disease. Sci. Adv. 6:eaba5933
    [Google Scholar]
  17. Chen G. 2021. In vivo confusion over in vivo conversion. Mol. Ther. 29:3097–98
    [Google Scholar]
  18. Chen W, Zheng Q, Huang Q, Ma S, Li M 2022. Repressing PTBP1 fails to convert reactive astrocytes to dopaminergic neurons in a 6-hydroxydopamine mouse model of Parkinson's disease. eLife 11:e75636
    [Google Scholar]
  19. Cheung HC, Hai T, Zhu W, Baggerly KA, Tsavachidis S et al. 2009. Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain 132:2277–88
    [Google Scholar]
  20. Contardo M, De Gioia R, Gagliardi D, Comi GP, Ottoboni L et al. 2022. Targeting PTB for glia-to-neuron reprogramming in vitro and in vivo for therapeutic development in neurological diseases. Biomedicines 10:399
    [Google Scholar]
  21. Dawlaty MM, Ganz K, Powell BE, Hu YC, Markoulaki S et al. 2011. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell 9:166–75
    [Google Scholar]
  22. de Alboran IM, O'Hagan RC, Gartner F, Malynn B, Davidson L et al. 2001. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14:45–55
    [Google Scholar]
  23. El-Brolosy MA, Stainier DYR. 2017. Genetic compensation: a phenomenon in search of mechanisms. PLOS Genet. 13:e1006780
    [Google Scholar]
  24. Escartin C, Galea E, Lakatos A, O'Callaghan JP, Petzold GC et al. 2021. Reactive astrocyte nomenclature, definitions, and future directions. Nat. Neurosci. 24:312–25
    [Google Scholar]
  25. Fang R, Xia C, Close JL, Zhang M, He J et al. 2022. Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH. Science 377:56–62
    [Google Scholar]
  26. Fischer KB, Collins HK, Callaway EM. 2019. Sources of off-target expression from recombinase-dependent AAV vectors and mitigation with cross-over insensitive ATG-out vectors. PNAS 116:27001–10
    [Google Scholar]
  27. Fu X, Zhu J, Duan Y, Li G, Cai H et al. 2020. Visual function restoration in genetically blind mice via endogenous cellular reprogramming. bioRxiv 2020.2004.2008.030981. https://doi.org/10.1101/2020.04.08.030981
  28. Galban S, Kuwano Y, Pullmann R Jr., Martindale JL, Kim HH et al. 2008. RNA-binding proteins HuR and PTB promote the translation of hypoxia-inducible factor 1α. Mol. Cell. Biol. 28:93–107
    [Google Scholar]
  29. Gao Z, Ure K, Ding P, Nashaat M, Yuan L et al. 2011. The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells. J. Neurosci. 31:9772–86
    [Google Scholar]
  30. Gascon S, Murenu E, Masserdotti G, Ortega F, Russo GL et al. 2016. Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming. Cell Stem Cell 18:396–409
    [Google Scholar]
  31. Georgilis A, Klotz S, Hanley CJ, Herranz N, Weirich B et al. 2018. PTBP1-mediated alternative splicing regulates the inflammatory secretome and the pro-tumorigenic effects of senescent cells. Cancer Cell 34:85–102.e109
    [Google Scholar]
  32. Gertz J, Savic D, Varley KE, Partridge EC, Safi A et al. 2013. Distinct properties of cell-type-specific and shared transcription factor binding sites. Mol. Cell 52:25–36
    [Google Scholar]
  33. Guo T, Pan X, Jiang G, Zhang D, Qi J et al. 2022. Downregulating PTBP1 fails to convert astrocytes into hippocampal neurons and to alleviate symptoms in Alzheimer's mouse models. J. Neurosci. 42:7309–17
    [Google Scholar]
  34. Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G 2014. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. Cell Stem Cell 14:188–202
    [Google Scholar]
  35. Han H, Best AJ, Braunschweig U, Mikolajewicz N, Li JD et al. 2022. Systematic exploration of dynamic splicing networks reveals conserved multistage regulators of neurogenesis. Mol. Cell 82:2982–99.e2914
    [Google Scholar]
  36. Heinrich C, Spagnoli FM, Berninger B. 2015. In vivo reprogramming for tissue repair. Nat. Cell Biol. 17:204–11
    [Google Scholar]
  37. Hensel JA, Nicholas S-AE, Kimble AL, Nagpal AS, Omar OMF et al. 2022. Splice factor polypyrimidine tract-binding protein 1 (Ptbp1) primes endothelial inflammation in atherogenic disturbed flow conditions. PNAS 119:e2122227119
    [Google Scholar]
  38. Herrero-Navarro Á, Puche-Aroca L, Moreno-Juan V, Sempere-Ferrandez A, Espinosa A et al. 2021. Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming. Sci. Adv. 7:eabe8978
    [Google Scholar]
  39. Higashi AY, Ikawa T, Muramatsu M, Economides AN, Niwa A et al. 2009. Direct hematological toxicity and illegitimate chromosomal recombination caused by the systemic activation of CreERT2. J. Immunol. 182:5633–40
    [Google Scholar]
  40. Hoang T, Kim DW, Appel H, Pannullo NA, Leavey P et al. 2021. Ptbp1 deletion does not induce glia-to-neuron conversion in adult mouse retina and brain. bioRxiv 2021.2010.2004.462784. https://doi.org/10.1101/2021.10.04.462784
  41. Hoang T, Kim DW, Appel H, Pannullo NA, Leavey P et al. 2022. Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina. Cell Rep. 39:110849
    [Google Scholar]
  42. Hu J, Qian H, Xue Y, Fu XD. 2018. PTB/nPTB: master regulators of neuronal fate in mammals. Biophys. Rep. 4:204–14
    [Google Scholar]
  43. Janbandhu VC, Moik D, Fassler R. 2014. Cre recombinase induces DNA damage and tetraploidy in the absence of loxP sites. Cell Cycle 13:462–70
    [Google Scholar]
  44. Johnson DS, Mortazavi A, Myers RM, Wold B. 2007. Genome-wide mapping of in vivo protein-DNA interactions. Science 316:1497–502
    [Google Scholar]
  45. Kettenmann H, Verkhratsky A. 2016. Glial cells: neuroglia. Neuroscience in the 21st Century DW Pfaff, ND Volkow 547–78. New York: Springer
    [Google Scholar]
  46. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT 2018. Inflammation as a central mechanism in Alzheimer's disease. Alzheimer's Dement. 4:575–90
    [Google Scholar]
  47. Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K et al. 2011. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8:200–13
    [Google Scholar]
  48. Kok FO, Shin M, Ni CW, Gupta A, Grosse AS et al. 2015. Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. Dev. Cell 32:97–108
    [Google Scholar]
  49. Kriegstein A, Alvarez-Buylla A. 2009. The glial nature of embryonic and adult neural stem cells. Annu. Rev. Neurosci. 32:149–84
    [Google Scholar]
  50. Laywell ED, Rakic P, Kukekov VG, Holland EC, Steindler DA. 2000. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. PNAS 97:13883–88
    [Google Scholar]
  51. Lee CM, Zhou L, Liu J, Shi J, Geng Y et al. 2020. Single-cell RNA-seq analysis revealed long-lasting adverse effects of tamoxifen on neurogenesis in prenatal and adult brains. PNAS 117:19578–89
    [Google Scholar]
  52. Leib D, Chen YH, Monteys AM, Davidson BL. 2022. Limited astrocyte-to-neuron conversion in the mouse brain using NeuroD1 overexpression. Mol. Ther. 30:982–86
    [Google Scholar]
  53. Lentini C, d'Orange M, Marichal N, Trottmann MM, Vignoles R et al. 2021. Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy. Cell Stem Cell 28:2104–21.e2110
    [Google Scholar]
  54. Li Q, Zheng S, Han A, Lin CH, Stoilov P et al. 2014. The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. eLife 3:e01201
    [Google Scholar]
  55. Liddelow SA, Barres BA. 2017. Reactive astrocytes: production, function, therapeutic potential. Immunity 46:957–67
    [Google Scholar]
  56. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ et al. 2017. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–87
    [Google Scholar]
  57. Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH. 2002. The adult substantia nigra contains progenitor cells with neurogenic potential. J. Neurosci. 22:6639–49
    [Google Scholar]
  58. Lin L, Zhang M, Stoilov P, Chen L, Zheng S 2020. Developmental attenuation of neuronal apoptosis by neural-specific splicing of Bak1 microexon. Neuron 107:1180–96.e1188
    [Google Scholar]
  59. Loonstra A, Vooijs M, Beverloo HB, Allak BA, van Drunen E et al. 2001. Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. PNAS 98:9209–14
    [Google Scholar]
  60. Ma S, Liu G, Sun Y, Xie J. 2007. Relocalization of the polypyrimidine tract-binding protein during PKA-induced neurite growth. Biochim. Biophys. Acta 1773:912–23
    [Google Scholar]
  61. Maimon R, Chillon-Marinas C, Snethlage CE, Singhal SM, McAlonis-Downes M et al. 2021. Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB. Nat. Neurosci. 24:1089–99
    [Google Scholar]
  62. Makeyev EV, Zhang J, Carrasco MA, Maniatis T. 2007. The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell. 27:435–48
    [Google Scholar]
  63. Martier R, Konstantinova P. 2020. Gene therapy for neurodegenerative diseases: slowing down the ticking clock. Front. Neurosci. 14:580179
    [Google Scholar]
  64. McGann JC, Spinner MA, Garg SK, Mullendorff KA, Woltjer RL, Mandel G. 2021. The genome-wide binding profile for human RE1 silencing transcription factor unveils a unique genetic circuitry in hippocampus. J. Neurosci. 41:6582–95
    [Google Scholar]
  65. Niu W, Zang T, Zou Y, Fang S, Smith DK et al. 2013. In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat. Cell Biol. 15:1164–75
    [Google Scholar]
  66. Pepin G, Ferrand J, Honing K, Jayasekara WS, Cain JE et al. 2016. Cre-dependent DNA recombination activates a STING-dependent innate immune response. Nucleic Acids Res. 44:5356–64
    [Google Scholar]
  67. Polydorides AD, Okano HJ, Yang YYL, Stefani G, Darnell RB. 2000. A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. PNAS 97:6350–55
    [Google Scholar]
  68. Powell SK, Khan N, Parker CL, Samulski RJ, Matsushima G et al. 2016. Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism. Gene Ther. 23:807–14
    [Google Scholar]
  69. Qian C, Dong B, Wang XY, Zhou FQ. 2021. In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system. FEBS J. 288:4773–85
    [Google Scholar]
  70. Qian H, Fu XD. 2021. Brain repair by cell replacement via in situ neuronal reprogramming. Annu. Rev. Genet. 55:45–69
    [Google Scholar]
  71. Qian H, Kang X, Hu J, Zhang D, Liang Z et al. 2020. Reversing a model of Parkinson's disease with in situ converted nigral neurons. Nature 582:550–56
    [Google Scholar]
  72. Robel S, Berninger B, Gotz M. 2011. The stem cell potential of glia: lessons from reactive gliosis. Nat. Rev. Neurosci. 12:88–104
    [Google Scholar]
  73. Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S et al. 2015. Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524:230–33
    [Google Scholar]
  74. Roussarie JP, Yao V, Rodriguez-Rodriguez P, Oughtred R, Rust J et al. 2020. Selective neuronal vulnerability in Alzheimer's disease: a network-based analysis. Neuron 107:821–35.e812
    [Google Scholar]
  75. Rowitch DH, Kriegstein AR. 2010. Developmental genetics of vertebrate glial-cell specification. Nature 468:214–22
    [Google Scholar]
  76. Shibasaki T, Tokunaga A, Sakamoto R, Sagara H, Noguchi S et al. 2013. PTB deficiency causes the loss of adherens junctions in the dorsal telencephalon and leads to lethal hydrocephalus. Cereb. Cortex 23:1824–35
    [Google Scholar]
  77. Shibayama M, Ohno S, Osaka T, Sakamoto R, Tokunaga A et al. 2009. Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation. FEBS J. 276:6658–68
    [Google Scholar]
  78. Si Z, Sun L, Wang X. 2021. Evidence and perspectives of cell senescence in neurodegenerative diseases. Biomed. Pharmacother. 137:111327
    [Google Scholar]
  79. Spellman R, Llorian M, Smith CW. 2007. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell 27:420–34
    [Google Scholar]
  80. Tai W, Wu W, Wang LL, Ni H, Chen C et al. 2021. In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury. Cell Stem Cell 28:923–37.e924
    [Google Scholar]
  81. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. 2022. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 22:657–73
    [Google Scholar]
  82. Tollervey JR, Wang Z, Hortobagyi T, Witten JT, Zarnack K et al. 2011. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Res. 21:1572–82
    [Google Scholar]
  83. Van den Berge K, Roux de Bezieux H, Street K, Saelens W, Cannoodt R et al. 2020. Trajectory-based differential expression analysis for single-cell sequencing data. Nat. Commun. 11:1201
    [Google Scholar]
  84. Vierbuchen T, Wernig M. 2012. Molecular roadblocks for cellular reprogramming. Mol. Cell 47:827–38
    [Google Scholar]
  85. Vuong CK, Black DL, Zheng S. 2016. The neurogenetics of alternative splicing. Nat. Rev. Neurosci. 17:265–81
    [Google Scholar]
  86. Vuong JK, Lin CH, Zhang M, Chen L, Black DL, Zheng S. 2016. PTBP1 and PTBP2 serve both specific and redundant functions in neuronal pre-mRNA splicing. Cell Rep. 17:2766–75
    [Google Scholar]
  87. Wang K, Pan S, Zhao P, Liu L, Chen Z et al. 2022. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 12:3847–61
    [Google Scholar]
  88. Wang LL, Serrano C, Zhong X, Ma S, Zou Y, Zhang CL. 2021. Revisiting astrocyte to neuron conversion with lineage tracing in vivo. Cell 184:5465–81
    [Google Scholar]
  89. Wang LL, Zhang CL. 2022. In vivo glia-to-neuron conversion: pitfalls and solutions. Dev. Neurobiol. 82:367–74
    [Google Scholar]
  90. Wei ZD, Shetty AK. 2021. Treating Parkinson's disease by astrocyte reprogramming: progress and challenges. Sci. Adv. 7:eabg3198
    [Google Scholar]
  91. Weinberg MS, Criswell HE, Powell SK, Bhatt AP, McCown TJ. 2017. Viral vector reprogramming of adult resident striatal oligodendrocytes into functional neurons. Mol. Ther. 25:928–34
    [Google Scholar]
  92. Wells JM, Watt FM. 2018. Diverse mechanisms for endogenous regeneration and repair in mammalian organs. Nature 557:322–28
    [Google Scholar]
  93. Xiang Z, Xu L, Liu M, Wang Q, Li W et al. 2021. Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex. Neural Regen. Res. 16:750–56
    [Google Scholar]
  94. Xie J, Lee JA, Kress TL, Mowry KL, Black DL. 2003. Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein. PNAS 100:8776–81
    [Google Scholar]
  95. Xie Y, Zhou J, Chen B 2022. Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina. Cell Rep. 39:110960
    [Google Scholar]
  96. Xu L, Xiang Z-Q, Guo Y-W, Xu Y-G, Liu M-H et al. 2022. Enhancing NeuroD1 expression to convert lineage-traced astrocytes into neurons. bioRxiv 2022.2006.2021.496971. https://doi.org/10.1101/2022.06.21.496971
  97. Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H et al. 2013. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 152:82–96
    [Google Scholar]
  98. Xue Y, Qian H, Hu J, Zhou B, Zhou Y et al. 2016. Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells. Nat. Neurosci. 19:807–15
    [Google Scholar]
  99. Xue Y, Zhou Y, Wu T, Zhu T, Ji X et al. 2009. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol. Cell 36:996–1006
    [Google Scholar]
  100. Yang G, Yan Z, Wu X, Zhang M, Xu C et al. 2022. Ptbp1 knockdown in mouse striatum did not induce astrocyte-to-neuron conversion using HA-tagged labeling system. bioRxiv 2022.2003.2029.486202. https://doi.org/10.1101/2022.03.29.486202
  101. Yang J, Zhou W, Zhang Y, Zidon T, Ritchie T, Engelhardt JF 1999. Concatemerization of adeno-associated virus circular genomes occurs through intermolecular recombination. J. Virol. 73:9468–77
    [Google Scholar]
  102. Yang RY, Chai R, Pan JY, Bao JY, Xia PH et al. 2023. Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury. Neural Regen. Res. 18:396–403
    [Google Scholar]
  103. Zhang M, Ergin V, Lin L, Stork C, Chen L, Zheng S 2019. Axonogenesis is coordinated by neuron-specific alternative splicing programming and splicing regulator PTBP2. Neuron 101:690–706.e610
    [Google Scholar]
  104. Zhang Y, Li B, Cananzi S, Han C, Wang LL et al. 2022. A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum. PNAS 119:e2107339119
    [Google Scholar]
  105. Zheng S, Gray EE, Chawla G, Porse BT, O'Dell TJ, Black DL. 2012. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat. Neurosci. 15:381–88
    [Google Scholar]
  106. Zhou H, Su J, Hu X, Zhou C, Li H et al. 2020. Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice. Cell 181:590–603
    [Google Scholar]
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