The p53 Pathway Controls SOX2-Mediated Reprogramming in the Adult Mouse Spinal Cord

Cell Reports

Volumn 17, Issue 3, 2016, Pages 891-903

  Wang, Lei Lei ^a   Su, Zhida ^a,b   Tai, Wenjiao ^a   Zou, Yuhua ^a   Xu, Xiao Ming ^c   Zhang, Chun Li ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b SECOND MILITARY MEDICAL UNIVERSITY   (China)

^c INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

adult neurogenesis; BDNF; in vivo reprogramming; neural progenitors; neural regeneration; noggin; p21; p53; SOX2; spinal cord injury

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; NOGGIN; PROTEIN P21; PROTEIN P53; TRANSCRIPTION FACTOR SOX2; TRANSCRIPTION FACTOR SOX;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CELL CYCLE; CELL MATURATION; CONTROLLED STUDY; FEMALE; GLIA CELL; GLUTAMATERGIC NEURON; MALE; MOUSE; NERVE CELL; NERVE REGENERATION; NEUROBLAST; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; SPINAL CORD; SPINAL CORD INJURY; AGING; ANIMAL; C57BL MOUSE; CELL DIFFERENTIATION; CELL PROLIFERATION; METABOLISM; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

AGING; ANIMALS; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLULAR MICROENVIRONMENT; CELLULAR REPROGRAMMING; MICE, INBRED C57BL; NEURONS; SIGNAL TRANSDUCTION; SOXB1 TRANSCRIPTION FACTORS; SPINAL CORD; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84992189476     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.09.038     Document Type: Article

References (59)

1. Abematsu, M., Tsujimura, K., Yamano, M., Saito, M., Kohno, K., Kohyama, J., Namihira, M., Komiya, S., Nakashima, K., Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. J. Clin. Invest. 120 (2010), 3255–3266.
2. Banito, A., Rashid, S.T., Acosta, J.C., Li, S., Pereira, C.F., Geti, I., Pinho, S., Silva, J.C., Azuara, V., Walsh, M., et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev. 23 (2009), 2134–2139.
3. Borgius, L., Nishimaru, H., Caldeira, V., Kunugise, Y., Löw, P., Reig, R., Itohara, S., Iwasato, T., Kiehn, O., Spinal glutamatergic neurons defined by EphA4 signaling are essential components of normal locomotor circuits. J. Neurosci. 34 (2014), 3841–3853.
4. Bradbury, E.J., McMahon, S.B., Spinal cord repair strategies: why do they work?. Nat. Rev. Neurosci. 7 (2006), 644–653.
5. Brugarolas, J., Chandrasekaran, C., Gordon, J.I., Beach, D., Jacks, T., Hannon, G.J., Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377 (1995), 552–557.
6. Buffelli, M., Burgess, R.W., Feng, G., Lobe, C.G., Lichtman, J.W., Sanes, J.R., Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424 (2003), 430–434.
7. Chi, L., Ke, Y., Luo, C., Li, B., Gozal, D., Kalyanaraman, B., Liu, R., Motor neuron degeneration promotes neural progenitor cell proliferation, migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice. Stem Cells 24 (2006), 34–43.
8. Courtine, G., Song, B., Roy, R.R., Zhong, H., Herrmann, J.E., Ao, Y., Qi, J., Edgerton, V.R., Sofroniew, M.V., Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 14 (2008), 69–74.
9. Dehmelt, L., Halpain, S., The MAP2/Tau family of microtubule-associated proteins. Genome Biol., 6, 2005, 204.
10. Fitch, M.T., Silver, J., CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209 (2008), 294–301.
11. Göritz, C., Dias, D.O., Tomilin, N., Barbacid, M., Shupliakov, O., Frisén, J., A pericyte origin of spinal cord scar tissue. Science 333 (2011), 238–242.
12. Gregorian, C., Nakashima, J., Le Belle, J., Ohab, J., Kim, R., Liu, A., Smith, K.B., Groszer, M., Garcia, A.D., Sofroniew, M.V., et al. Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis. J. Neurosci. 29 (2009), 1874–1886.
13. Groszer, M., Erickson, R., Scripture-Adams, D.D., Lesche, R., Trumpp, A., Zack, J.A., Kornblum, H.I., Liu, X., Wu, H., Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294 (2001), 2186–2189.
14. Guo, S., Zi, X., Schulz, V.P., Cheng, J., Zhong, M., Koochaki, S.H., Megyola, C.M., Pan, X., Heydari, K., Weissman, S.M., et al. Nonstochastic reprogramming from a privileged somatic cell state. Cell 156 (2014), 649–662.
15. 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 14 (2014), 188–202.
16. Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C.J., Creyghton, M.P., van Oudenaarden, A., Jaenisch, R., Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462 (2009), 595–601.
17. Heinrich, C., Bergami, M., Gascón, S., Lepier, A., Viganò, F., Dimou, L., Sutor, B., Berninger, B., Götz, M., Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Reports 3 (2014), 1000–1014.
18. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., Yamanaka, S., Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460 (2009), 1132–1135.
19. Horky, L.L., Galimi, F., Gage, F.H., Horner, P.J., Fate of endogenous stem/progenitor cells following spinal cord injury. J. Comp. Neurol. 498 (2006), 525–538.
20. Horner, P.J., Power, A.E., Kempermann, G., Kuhn, H.G., Palmer, T.D., Winkler, J., Thal, L.J., Gage, F.H., Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci. 20 (2000), 2218–2228.
21. Islam, M.M., Smith, D.K., Niu, W., Fang, S., Iqbal, N., Sun, G., Shi, Y., Zhang, C.L., Enhancer analysis unveils genetic interactions between TLX and SOX2 in neural stem cells and in vivo reprogramming. Stem Cell Reports 5 (2015), 805–815.
22. Jessberger, S., Gage, F.H., Adult neurogenesis: bridging the gap between mice and humans. Trends Cell Biol. 24 (2014), 558–563.
23. Jiang, H., Xu, Z., Zhong, P., Ren, Y., Liang, G., Schilling, H.A., Hu, Z., Zhang, Y., Wang, X., Chen, S., et al. Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons. Nat. Commun., 6, 2015, 10100.
24. Johansson, C.B., Momma, S., Clarke, D.L., Risling, M., Lendahl, U., Frisén, J., Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96 (1999), 25–34.
25. Kawamura, T., Suzuki, J., Wang, Y.V., Menendez, S., Morera, L.B., Raya, A., Wahl, G.M., Izpisúa Belmonte, J.C., Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460 (2009), 1140–1144.
26. Kempermann, G., Song, H., Gage, F.H., Neurogenesis in the adult hippocampus. Cold Spring Harb. Perspect. Biol., 7, 2015, a018812.
27. Komarov, P.G., Komarova, E.A., Kondratov, R.V., Christov-Tselkov, K., Coon, J.S., Chernov, M.V., Gudkov, A.V., A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285 (1999), 1733–1737.
28. Lane, D., Levine, A., p53 Research: the past thirty years and the next thirty years. Cold Spring Harb. Perspect. Biol., 2, 2010, a000893.
29. Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M.A., Serrano, M., The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460 (2009), 1136–1139.
30. Li, S., Sun, G., Murai, K., Ye, P., Shi, Y., Characterization of TLX expression in neural stem cells and progenitor cells in adult brains. PLoS ONE, 7, 2012, e43324.
31. Lim, D.A., Alvarez-Buylla, A., The adult ventricular–subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb. Perspect. Biol., 2016, 10.1101/cshperspect.a018820.
32. Liu, Y., Miao, Q., Yuan, J., Han, S., Zhang, P., Li, S., Rao, Z., Zhao, W., Ye, Q., Geng, J., et al. Ascl1 converts dorsal midbrain astrocytes into functional neurons in vivo. J. Neurosci. 35 (2015), 9336–9355.
33. Llewellyn-Smith, I.J., Martin, C.L., Fenwick, N.M., Dicarlo, S.E., Lujan, H.L., Schreihofer, A.M., VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. J. Comp. Neurol. 503 (2007), 741–767.
34. Lugert, S., Vogt, M., Tchorz, J.S., Müller, M., Giachino, C., Taylor, V., Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1(high) intermediate progenitors. Nat. Commun., 3, 2012, 670.
35. Madisen, L., Zwingman, T.A., Sunkin, S.M., Oh, S.W., Zariwala, H.A., Gu, H., Ng, L.L., Palmiter, R.D., Hawrylycz, M.J., Jones, A.R., et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13 (2010), 133–140.
36. Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J., Berns, A., Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14 (2000), 994–1004.
37. Marión, R.M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., Blasco, M.A., A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460 (2009), 1149–1153.
38. Mullen, R.J., Buck, C.R., Smith, A.M., NeuN, a neuronal specific nuclear protein in vertebrates. Development 116 (1992), 201–211.
39. Nishimaru, H., Kakizaki, M., The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cord. Acta Physiol. (Oxf.) 197 (2009), 83–97.
40. Niu, W., Zou, Y., Shen, C., Zhang, C.L., Activation of postnatal neural stem cells requires nuclear receptor TLX. J. Neurosci. 31 (2011), 13816–13828.
41. Niu, W., Zang, T., Zou, Y., Fang, S., Smith, D.K., Bachoo, R., Zhang, C.L., In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat. Cell Biol. 15 (2013), 1164–1175.
42. Niu, W., Zang, T., Smith, D.K., Vue, T.Y., Zou, Y., Bachoo, R., Johnson, J.E., Zhang, C.L., SOX2 reprograms resident astrocytes into neural progenitors in the adult brain. Stem Cell Reports 4 (2015), 780–794.
43. Ohori, Y., Yamamoto, S., Nagao, M., Sugimori, M., Yamamoto, N., Nakamura, K., Nakafuku, M., Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord. J. Neurosci. 26 (2006), 11948–11960.
44. Pechnick, R.N., Zonis, S., Wawrowsky, K., Pourmorady, J., Chesnokova, V., p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Proc. Natl. Acad. Sci. USA 105 (2008), 1358–1363.
45. Rossignol, S., Schwab, M., Schwartz, M., Fehlings, M.G., Spinal cord injury: time to move?. J. Neurosci. 27 (2007), 11782–11792.
46. Scholzen, T., Gerdes, J., The Ki-67 protein: from the known and the unknown. J. Cell. Physiol. 182 (2000), 311–322.
47. Sellers, D.L., Maris, D.O., Horner, P.J., Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury. J. Neurosci. 29 (2009), 6722–6733.
48. Shechter, R., Ziv, Y., Schwartz, M., New GABAergic interneurons supported by myelin-specific T cells are formed in intact adult spinal cord. Stem Cells 25 (2007), 2277–2282.
49. Shihabuddin, L.S., Horner, P.J., Ray, J., Gage, F.H., Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J. Neurosci. 20 (2000), 8727–8735.
50. Sofroniew, M.V., Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 32 (2009), 638–647.
51. Su, Z., Niu, W., Liu, M.L., Zou, Y., Zhang, C.L., In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat. Commun., 5, 2014, 3338.
52. Sun, G., Yu, R.T., Evans, R.M., Shi, Y., Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc. Natl. Acad. Sci. USA 104 (2007), 15282–15287.
53. Thuret, S., Moon, L.D., Gage, F.H., Therapeutic interventions after spinal cord injury. Nat. Rev. Neurosci. 7 (2006), 628–643.
54. Torper, O., Pfisterer, U., Wolf, D.A., Pereira, M., Lau, S., Jakobsson, J., Björklund, A., Grealish, S., Parmar, M., Generation of induced neurons via direct conversion in vivo. Proc. Natl. Acad. Sci. USA 110 (2013), 7038–7043.
55. Torper, O., Ottosson, D.R., Pereira, M., Lau, S., Cardoso, T., Grealish, S., Parmar, M., In vivo reprogramming of striatal NG2 glia into functional neurons that integrate into local host circuitry. Cell Rep. 12 (2015), 474–481.
56. Utikal, J., Polo, J.M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R.M., Khalil, A., Rheinwald, J.G., Hochedlinger, K., Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460 (2009), 1145–1148.
57. Vessal, M., Aycock, A., Garton, M.T., Ciferri, M., Darian-Smith, C., Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transection. Eur. J. Neurosci. 26 (2007), 2777–2794.
58. Yang, H., Lu, P., McKay, H.M., Bernot, T., Keirstead, H., Steward, O., Gage, F.H., Edgerton, V.R., Tuszynski, M.H., Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury. J. Neurosci. 26 (2006), 2157–2166.
59. Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., Zhang, Q., Xiang, C., Hou, P., Song, Z., et al. Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3 (2008), 475–479.