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Molecular and Cellular Mechanisms Regulating Quiescence and Division of Hippocampal Stem Cells

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Abstract—Neurogenesis in the dentate gyrus of the hippocampus occurs throughout the life of mammals, including humans. A common view is that integration of newborn neurons provides a high level of plasticity in the hippocampal neuronal network. This is important for cognitive brain function, memory formation, and emotions. Neurogenesis is supported by the pool of stem cells located in the subgranular zone of the dentate gyrus. These cells spend most of their life in a state of mitotic quiescence. During aging, the reservoir of stem cells gradually decreases due to division and irreversible differentiation into astrocytes. The kinetics of spending the pool of stem cells is determined by the balance between quiescence and division. The question on the molecular mechanisms regulating this balance is one of the key issues in the biology of brain stem cells. This is important not only in order to understand the fundamental principles of regulation of neurogenesis, but also in developing new strategies for using the internal reservoir of stem cells to ameliorate hippocampal plasticity deficit in various brain pathologies and aging. To date a lot of new and interesting data have been accumulated on multiple mechanisms involved in the regulation of stem cell quiescence and division. In this review, we overview current knowledge on the signal molecules and cellular receptors participating in the maintenance of the quiescent state of stem cells, the mechanisms of the shift from the quiescent state to proliferation at the level of gene transcription, and the roles of components of the stem cell niche, such as neuronal connections, macro- and microglia, and the extracellular matrix, in the regulation of the balance between quiescence and division of stem cells and in the maintenance and exhaustion of their pool.

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REFERENCES

  1. Gould, E., Reeves, A.J., Fallah, M., Tanapat, P., Gross, C.G., and Fuchs, E., Proc. Natl. Acad. Sci. USA, 1999, vol. 96, no. 9, pp. 5263–5267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kuhn, H.G., Dickinson-Anson, H., and Gage, F.H., J. Neurosci., 1996, vol. 16, no. 6, pp. 2027–2033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Siwak-Tapp, C.T., Head, E., Muggenburg, B.A., Milgram, N.W., and Cotman, C.W., Neurobiol. Learn. Mem., 2007, vol. 88, no. 2, pp. 249–259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Van Praag, H., Schinder, A.F., Christle, B.R., Toni, N., Palmer, T.D., and Gage, F.H., Nature, 2002, vol. 415, no. 6875, pp. 1030–1034.

    Article  CAS  PubMed  Google Scholar 

  5. Boldrini, M., Fulmore, C.A., Tartt, A.N., Simeon, L.R., Pavlova, I., Poposka, V., Rosoklija, G.B., Stankov, A., Arango, V., Dwork, A.J., Hen, R., and Mann, J.J., Cell, 2018, vol. 22, no. 4, pp. 589–599.

    CAS  Google Scholar 

  6. Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A., and Gage, F.H., Nat. Med., 1998, vol. 4, no. 11, pp. 1313–1317.

    Article  CAS  PubMed  Google Scholar 

  7. Knoth, R., Singec, I., Ditter, M., Pantazis, G., Capetian, P., Meyer, R.P., Horvat, V., Volk, B., and Kempermann, G., PLoS One, 2010, vol. 5, no. 1, p. e8809.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Moreno-Jiménez, E.P., Flor-García, M., Terreros-Roncal, J., Rábano, A., Cafini, F., Pallas-Bazarra, N., Ávila, J., and Llorens-Martín, M., Nat. Med., 2019, vol. 25, no. 4, pp. 554–560.

    Article  PubMed  CAS  Google Scholar 

  9. Spalding, K.L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H.B., Boström, E., Westerlund, I., Vial, C., Buchholz, B.A., Possnert, G., Mash, D.C., Druid, H., and Frisén, J., Cell, 2013, vol. 153, no. 6, p. 1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tobin, M.K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W.G., Kim, N., Dawe, R.J., Bennett, D.A., Arfanakis, K., and Lazarov, O., Cell Stem Cell., 2019, vol. 24, no. 6, pp. 974–982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Altman, J., Science, 1962, vol. 135, no. 3509, pp. 1127–1128.

    Article  CAS  PubMed  Google Scholar 

  12. Altman, J., Anat. Rec., 1963, vol. 145, no. 4, pp. 573–591.

    Article  CAS  PubMed  Google Scholar 

  13. Altman, J. and Das, G.D., J. Comp. Neurol., 1965, vol. 124, no. 3, pp. 319–335.

    Article  CAS  PubMed  Google Scholar 

  14. Anacker, C. and Hen, R., Nat. Rev. Neurosci., 2017, vol. 18, no. 6, pp. 335–346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gonçalves, J.T., Schafer, S.T., and Gage, F.H., Cell, 2016, vol. 167, no. 4, pp. 897–914.

    Article  PubMed  CAS  Google Scholar 

  16. Schoenfeld, T.J. and Cameron, H.A., Neuropsychopharmacology, 2015, vol. 40, no. 1, pp. 113–128.

    Article  PubMed  Google Scholar 

  17. Snyder, J.S., Soumier, A., Brewer, M., Pickel, J., and Cameron, H.A., Nature, 2011, vol. 476, no. 7361, pp. 458–462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saxe, M.D., Battaglia, F., Wang, J.W., Malleret, G., David, D.J., Monckton, J.E., Garcia, A.D.R., Sofroniew, M.V., Kandel, E.R., Santarelli, L., Hen, R., and Drew, M.R., Proc. Natl. Acad. Sci. USA, 2006, vol. 103, no. 46, pp. 17501–17506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tunc-Ozcan, E., Peng, C.Y., Zhu, Y., Dunlop, S.R., Contractor, A., and Kessler, J.A., Nat. Commun., 2019, vol. 10, no. 1, pp. 1–9.

    Article  CAS  Google Scholar 

  20. Nakashiba, T., Cushman, J.D., Pelkey, K.A., Renaudineau, S., Buhl, D.L., McHugh, T.J., Barrera, V.R., Chittajallu, R., Iwamoto, K.S., McBain, C.J., Fanselow, M.S., and Tonegawa, S., Cell, 2012, vol. 149, no. 1, pp. 188–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sahay, A., Scobie, K.N., Hill, A.S., O’Carroll, C.M., Kheirbek, M.A., Burghardt, N.S., Fenton, A.A., Dranovsky, A., and Hen, R., Nature, 2011, vol. 472, no. 7344, pp. 466–470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Anderson, M.L., Sisti, H.M., Curlik, D.M., and Shors, T.J., Eur. J. Neurosci., 2011, vol. 33, no. 1, pp. 175–181.

    Article  PubMed  Google Scholar 

  23. Encinas, J.M., Hamani, C., Lozano, A.M., and Enikolopov, G., J. Comp. Neurol., 2011, vol. 519, no. 1, pp. 6–20.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gould, E., Beylin, A., Tanapat, P., Reeves, A., and Shors, T.J., Nat. Neurosci., 1999, vol. 2, no. 3, pp. 260–265.

    Article  CAS  PubMed  Google Scholar 

  25. Malberg, J.E., Eisch, A.J., Nestler, E.J., and Duman, R.S., J. Neurosci., 2000, vol. 20, no. 24, pp. 9104–9110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., Belzung, C., and Hen, R., Science, 2003, vol. 301, no. 5634, pp. 805–809.

    Article  CAS  PubMed  Google Scholar 

  27. Van Praag, H., Kempermann, G., and Gage, F.H., Nat. Neurosci., 1999, vol. 2, no. 3, pp. 266–270.

    Article  CAS  PubMed  Google Scholar 

  28. Veena, J., Srikumar, B.N., Mahati, K., Bhagya, V., Raju, T.R., and Shankaranarayana Rao, B.S., J. Neurosci. Res., 2009, vol. 87, no. 4, pp. 831–843.

    Article  CAS  PubMed  Google Scholar 

  29. Gould, E., McEwen, B.S., Tanapat, P., Galea, L.A.M., and Fuchs, E., J. Neurosci., 1997, vol. 17, no. 7, pp. 2492–2498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ngwenya, L.B. and Danzer, S.C., Front. Neurosci., 2019, vol. 13, no. 1014, pp. 1–8.

    Google Scholar 

  31. Pereira, DiasG., Hollywood, R., Bevilaqua, M.C., Luz, A.C.D., Hindges, R., Nardi, A.E., and Thuret, S., Neuro Oncol., 2014, vol. 16, no. 4, pp. 476–492.

    Article  Google Scholar 

  32. Raber, J., Rola, R., LeFevour, A., Morhardt, D., Curley, J., Mizumatsu, S., Vandenberg, S.R., and Fike, J.R., Radiat. Res., 2004, vol. 162, no. 1, pp. 39–47.

    Article  CAS  PubMed  Google Scholar 

  33. Reif, A., Fritzen, S., Finger, M., Strobel, A., Lauer, M., Schmitt, A., and Lesch, K.P., Mol. Psychiatry, 2006, vol. 11, no. 5, pp. 514–522.

    Article  CAS  PubMed  Google Scholar 

  34. Sahay, A. and Hen, R., Growth Factors and Psychiatric Disorders, 2008, vol. 289, pp. 152–160.

    Article  CAS  Google Scholar 

  35. Marxreiter, F., Regensburger, M., and Winkler, J., CMLS, vol. 70, no. 3, pp. 459–473.

  36. Woitke, F., Ceanga, M., Rudolph, M., Niv, F., Witte, O.W., Redecker, C., Kunze, A., and Keiner, S., PLoS One, 2017, vol. 12, no. 9, p. e0183463.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Drew, M. and Hen, R., CNS Neurol. Disord., 2008, vol. 6, no. 3, pp. 205–218.

    Article  Google Scholar 

  38. Miller, B.R. and Hen, R., Curr. Opin. Neurobiol., 2015, vol. 30, pp. 51–58.

    Article  CAS  PubMed  Google Scholar 

  39. Erickson, C.A. and Barnes, C.A., Exp. Geront., 2003, vol. 38, nos. 1–2, pp. 61–69.

    Article  CAS  Google Scholar 

  40. Kronenberg, G., Bick-Sander, A., Bunk, E., Wolf, C., Ehninger, D., and Kempermann, G., Neurobiol. Aging, 2006, vol. 27, no. 10, pp. 1505–1513.

    Article  PubMed  Google Scholar 

  41. Sun, D., Chen, J., Bao, X., Cai, Y., Zhao, J., Huang, J., Huang, W., Fan, X., Xu, H., Mol. Neurobiol., 2015, vol. 52, no. 1, pp. 464–477.

    Article  CAS  PubMed  Google Scholar 

  42. Jonas, P. and Lisman, J., Front. Neural Circuits, 2014, vol. 8, p. 107.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K., Ikeda, T., Itohara, S., and Kageyama, R., Nat. Neurosci., 2008, vol. 11, no. 10, pp. 1153–1161.

    Article  CAS  PubMed  Google Scholar 

  44. Ninkovic, J., Mori, T., and Götz, M., J. Neurosci., 2007, vol. 27, no. 40, pp. 10906–10911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Seri, B., García-Verdugo, J.M., McEwen, B.S., and Alvarez-Buylla, A., J. Neurosci., 2001, vol. 21, no. 18, pp. 7153–7160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kempermann, G., Jessberger, S., Steiner, B., and Kronenberg, G., Trends Neurosci., 2004, vol. 27, no. 8, pp. 447–452.

    Article  CAS  PubMed  Google Scholar 

  47. Lugert, S., Basak, O., Knuckles, P., Haussler, U., Fabel, K., Götz, M., Haas, C.A., Kempermann, G., Taylor, V., and Giachino, C., Cell Stem Cell, 2010, vol. 6, no. 5, pp. 445–456.

    Article  CAS  PubMed  Google Scholar 

  48. Bonaguidi, M.A., Wheeler, M.A., Shapiro, J.S., Stadel, R.P., Sun, G.J., Ming, G.L., and Song, H., Cell, 2011, vol. 145, no. 7, pp. 1142–1155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Encinas, J.M., Michurina, T.V., Peunova, N., Park, J.H., Tordo, J., Peterson, D.A., Fishell, G., Koulakov, A., and Enikolopov, G., Cell Stem Cell, 2011, vol. 8, no. 5, pp. 566–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mignone, J.L., Kukekov, V., Chiang, A.S., Steindler, D., and Enikolopov, G., J. Comp. Neurol., 2004, vol. 469, no. 3, pp. 311–324.

    Article  CAS  PubMed  Google Scholar 

  51. Sierra, A., Martin-Suárez, S., Valcárcel-Martín, R., Pascual-Brazo, J., Aelvoet, S.A., Abiega, O., Deudero, J.J., Brewster, A.L., Bernales, I., Anderson, A.E., Baekelandt, V., Maletić-Savatić, M., and Encinas, J.M., Cell Stem Cell, 2015, vol. 16, no. 5, pp. 488–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gebara, E., Bonaguidi, M.A., Beckervordersandforth, R., Sultan, S., Udry, F., Gijs, P.J., Lie, D.C., Ming, G.L., Song, H., and Toni, N., Stem Cells, 2016, vol. 34, no. 4, pp. 997–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Moss, J., Gebara, E., Bushong, E.A., Sánchez-Pascual, I., O’Laoi, R., El M’Gharia, I., Kocher-Braissant, J., Ellisman, M.H., and Toni, N., Proc. Natl. Acad. Sci. USA, 2016, vol. 113, no. 18, pp. E2536–E2545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shtaya, A., Sadek, A.R., Zaben, M., Seifert, G., Pringle, A., Steinhauser, C., and Gray, W.P., Glia, 2018, vol. 66, no. 11, pp. 2397–2413.

    Article  PubMed  Google Scholar 

  55. Nicola, Z., Fabel, K., and Kempermann, G., Front. Neuroanat., 2015, vol. 9, no. 53, pp. 1–13.

    Article  Google Scholar 

  56. Suh, H., Consiglio, A., Ray, J., Sawai, T., D’Amour, K.A., and Gage, F.H.H., Cell Stem Cell, 2007, vol. 1, no. 5, pp. 515–528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lazutkin, A., Podgorny, O., and Enikolopov, G., Behav. Brain Res., 2019, vol. 374, pp. 112–118.

    Article  CAS  Google Scholar 

  58. Brandt, M.D., Jessberger, S., Steiner, B., Kronenberg, G., Reuter, K., Bick-Sander, A., Von der Behrens, W., and Kempermann, G., Mol. Cell. Neurosci., 2003, vol. 24, no. 3, pp. 603–613.

    Article  CAS  PubMed  Google Scholar 

  59. Hattiangady, B. and Shetty, A.K., Neurobiol. Aging, 2008, vol. 29, no. 1, pp. 129–147.

    Article  CAS  PubMed  Google Scholar 

  60. Mineyeva, O.A., Enikolopov, G., and Koulakov, A.A., Sci. Rep., vol. 8, no. 1, pp. 1–12.

  61. Namba, T., Maekawa, M., Yuasa, S., Kohsaka, S., and Uchino, S., Glia, 2009, vol. 57, no. 10, pp. 1082–1090.

    Article  PubMed  Google Scholar 

  62. Urbán, N., Van Den, BergD.L.C., Forget, A., Andersen, J., Demmers, J.A.A., Hunt, C., Ayrault, O., and Guillemot, F., Science, 2016, vol. 353, no. 6296, pp. 292–295.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Pilz, G.A., Bottes, S., Betizeau, M., Jörg, D.J., Carta, S., Simons, B.D., Helmchen, F., and Jessberger, S., Science, 2018, vol. 359, no. 6376, pp. 658–662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sierra, A., Encinas, J.M., Deudero, J.J.P., Chancey, J.H., Enikolopov, G., Overstreet-Wadiche, L.S., Tsirka, S.E., and Maletic-Savatic, M., Cell Stem Cell, 2010, vol. 7, no. 4, pp. 483–495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Segi-Nishida, E., Warner-Schmidt, J.L., and Duman, R.S., Proc. Natl. Acad. Sci. USA, 2008, vol. 105, no. 32, pp. 11352–11357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cheung, T.H. and Rando, T.A., Nat. Rev. Mol. Cell Biol., 2013, vol. 14, no. 6, pp. 329–340.

    Article  CAS  PubMed  Google Scholar 

  67. Dhawan, J. and Rando, T.A., Trends Cell Biol., 2005, vol. 15, no. 12, pp. 666–673.

    Article  CAS  PubMed  Google Scholar 

  68. Lay, K., Kume, T., and Fuchs, E., Proc. Natl. Acad. Sci. USA, 2016, vol. 113, no. 11, pp. 1506–1515.

    Article  CAS  Google Scholar 

  69. Wilson, A., Laurenti, E., Oser, G., van der Wath, R.C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C.F., Eshkind, L., Bockamp, E., Lió, P., MacDonald, H.R., and Trumpp, A., Cell, 2008, vol. 135, no. 6, pp. 1118–1129.

    Article  CAS  PubMed  Google Scholar 

  70. Clevers, H., Cell, 2013, vol. 154, no. 2, p. 274.

    Article  CAS  PubMed  Google Scholar 

  71. Li, N. and Clevers, H., Science, 2010, vol. 327, no. 5965, pp. 542–545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Andersen, J., Úrban, N., Achimastou, A., Ito, A., Simic, M., Ullom, K., Martynoga, B., Lebel, M., Göritz, C., Frisén, J., Nakafuku, M., and Guillemot, F., Neuron, 2014, vol. 83, no. 5, pp. 1085–1097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Furutachi, S., Matsumoto, A., Nakayama, K.I., and Gotoh, Y., EMBO J., 2013, vol. 32, no. 7, pp. 970–981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Jones, K.M., Saric, N., Russell, J.P., Andoniadou, C.L., Scambler, P.J., and Basson, M.A., Stem Cells, 2015, vol. 33, no. 1, pp. 196–210.

    Article  CAS  PubMed  Google Scholar 

  75. Knobloch, M., Pilz, G.A., Ghesquière, B., Kovacs, W.J., Wegleiter, T., Moore, D.L., Hruzova, M., Zamboni, N., Carmeliet, P., and Jessberger, S., Cell Rep., 2017, vol. 20, no. 9, pp. 2144–2155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhou, Y., Bond, A.M., Shade, J.E., Zhu, Y., Davis, C.-H.O., Wang, X., Su, Y., Yoon, K.-J., Phan, A.T., Chen, W.J., Oh, J.H., Marsh-Armstrong, N., Atabai, K., Ming, G.-L., and Song, H., Cell Stem Cell, 2018, vol. 23, no. 3, pp. 444–452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Urbach, A. and Witte, O.W., Front. Cell Dev. Biol., 2019, vol. 7, no. 55, pp. 1–22.

    Article  Google Scholar 

  78. Cope, E.C. and Gould, E., Cell Stem Cell, 2019, vol. 24, no. 5, pp. 690–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mira, H., Andreu, Z., Suh, H., Chichung, LieD., Jessberger, S., Consiglio, A., Emeterio, J.S., Hortigüela, R., Marqués-Torrejón, M.A., Nakashima, K., Colak, D., Götz, M., Fariñas, I., and Gage, F.H., Cell Stem Cell, 2010, vol. 7, no. 1, pp. 78–89.

    Article  CAS  PubMed  Google Scholar 

  80. Song, J., Zhong, C., Bonaguidi, M.A., Sun, G.J., Hsu, D., Gu, Y., Meletis, K., Huang, Z.J., Ge, S., Enikolopov, G., Deisseroth, K., Luscher, B., Christian, K.M., Ming, G.L., and Song, H., Nature, 2012, vol. 489, no. 7414, pp. 150–154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yeh, C.Y., Asrican, B., Moss, J., Quintanilla, L.J., He, T., Mao, X., Cassé, F., Gebara, E., Bao, H., Lu, W., Toni, N., and Song, J., Neuron, 2018, vol. 99, no. 3, pp. 493–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Berg, D.A., Su, Y., Jimenez-Cyrus, D., Patel, A., Huang, N., Morizet, D., Lee, S., Shah, R., Ringeling, F.R., Jain, R., Epstein, J.A., Wu, Q.F., Canzar, S., Ming, G.L., Song, H., and Bond, A.M., Cell, 2019, vol. 177, no. 3, pp. 654–668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shin, J., Berg, D.A., Zhu, Y., Shin, J.Y., Song, J., Bonaguidi, M.A., Enikolopov, G., Nauen, D.W., Christian, K.M., Ming, G.L., and Song, H., Cell Stem Cell, 2015, vol. 17, no. 3, pp. 360–372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Walker, T.L., Overall, R.W., Vogler, S., Sykes, A.M., Ruhwald, S., Lasse, D., Ichwan, M., Fabel, K., and Kempermann, G., Stem Cell Rep., 2016, vol. 6, no. 4, pp. 552–565.

    Article  CAS  Google Scholar 

  85. Ehm, O., Göritz, C., Covic, M., Schäffner, I., Schwarz, T.J., Karaca, E., Kempkes, B., Kremmer, E., Pfrieger, F.W., Espinosa, L., Bigas, A., Giachino, C., Taylor, V., Frisén, J., and Lie, D.C., J. Neurosci., 2010, vol. 30, no. 41, pp. 13794–13807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kang, W. and Hébert, J.M., J. Neurosci., 2015, vol. 35, no. 28, pp. 10217–10223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lie, D.C., Colamarino, S.A., Song, H.J., Désiré, L., Mira, H., Consiglio, A., Lein, E.S., Jessberger, S., Lansford, H., Dearie, A.R., and Gage, F.H., Nature, 2005, vol. 437, no. 7063, pp. 1370–1375.

    Article  CAS  PubMed  Google Scholar 

  88. Mukherjee, S., Brulet, R., Zhang, L., and Hsieh, J., Nat. Commun., 2016, vol. 7, no. 1, pp. 1–14.

    CAS  Google Scholar 

  89. Llorens-Bobadilla, E., Zhao, S., Baser, A., Saiz-Castro, G., Zwadlo, K., and Martin-Villalba, A., Cell Stem Cell, 2015, vol. 17, no. 3, pp. 329–340.

    Article  CAS  PubMed  Google Scholar 

  90. Matsushime, H., Roussel, M.F., Ashmun, R.A., and Sherr, C.J., Cell, 1991, vol. 65, no. 4, pp. 701–713.

    Article  CAS  PubMed  Google Scholar 

  91. Matsushime, H., Quelle, D.E., Shurtleff, S.A., Shibuya, M., Sherr, C.J., and Kato, J.Y., Mol. Cell. Biol., 1994, vol. 14, no. 3, pp. 2066–2076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Matsushime, H., Ewen, M.E., Strom, D.K., Kato, J.Y., Hanks, S.K., Roussel, M.F., and Sherr, C.J., Cell, 1992, vol. 71, no. 2, pp. 323–334.

    Article  CAS  PubMed  Google Scholar 

  93. Meyerson, M. and Harlow, E., Mol. Cell. Biol., 1994, vol. 14, no. 3, pp. 2077–2086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Sherr, C.J. and Roberts, J.M., Genes Dev., 2004, vol. 18, no. 22, pp. 2699–2711.

    Article  CAS  PubMed  Google Scholar 

  95. Kowalczyk, A., Filipkowski, R.K., Rylski, M., Wilczynski, G.M., Konopacki, F.A., Jaworski, J., Ciemerych, M.A., Sicinski, P., and Kaczmarek, L., J. Cell Biol., 2004, vol. 167, no. 2, pp. 209–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ansorg, A., Witte, O.W., and Urbach, A., BMC Neurosci., 2012, vol. 13, no. 1, p. 46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Artegiani, B., Lindemann, D., and Calegari, F., J. Exp. Med., 2011, vol. 208, no. 5, pp. 937–948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Berdugo-Vega, G., Arias-Gil, G., López-Fernández, A., Artegiani, B., Wasielewska, J.M., Lee, C.C., Lippert, M.T., Kempermann, G., Takagaki, K., and Calegari, F., Nat. Commun., 2020, vol. 11, no. 1, pp. 1–12.

    Google Scholar 

  99. Le, O., Palacio, L., Bernier, G., Batinic-Haberle, I., Hickson, G., and Beauséjour, C., Stem Cell Rep., 2018, vol. 10, no. 6, pp. 1721–1733.

    Article  CAS  Google Scholar 

  100. Pechnick, R.N., Zonis, S., Wawrowsky, K., Pourmorady, J., and Chesnokova, V., Proc. Natl. Acad. Sci. USA, 2008, vol. 105, no. 4, pp. 1358–1363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Qiu, J., Takagi, Y., Harada, J., Topalkara, K., Wang, Y., Sims, J.R., Zheng, G., Huang, P., Ling, Y., Scadden, D.T., Moskowitz, M.A., and Cheng, T., Stem Cells, 2009, vol. 27, no. 4, pp. 920–927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Andreu, Z., Khan, M.A., González-Gõmez, P., Negueruela, S., Hortigüela, R., San Emeterio, J., Ferrõn, S.R., Martínez, G., Vidal, A., Fariñas, I., Lie, D.C., and Mira, H., Stem Cells, 2015, vol. 33, no. 1, pp. 219–229.

    Article  CAS  PubMed  Google Scholar 

  103. Morales, A.V. and Mira, H., Front. Cell Dev. Biol., 2019, vol. 7, no. 96, pp. 1–10.

    Article  Google Scholar 

  104. Jessberger, S., Toni, N., Clemenson, G.D., Ray, J., and Gage, F.H., Nat. Neurosci., 2008, vol. 11, no. 8, pp. 888–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., and Kageyama, R., J. Neurosci., 2010, vol. 30, no. 9, pp. 3489–3498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Sueda, R., Imayoshi, I., Harima, Y., and Kageyama, R., Genes Dev., 2019, vol. 33, nos. 9–10, pp. 511–523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Froyen, G., Corbett, M., Vandewalle, J., Jarvela, I., Lawrence, O., Meldrum, C., Bauters, M., Govaerts, K., Vandeleur, L., Van Esch, H., Chelly, J., Sanlaville, D., van Bokhoven, H., Ropers, H.H., Laumonnier, F., Ranieri, E., Schwartz, C.E., Abidi, F., Tarpey, P.S., et al., Am. J. Hum. Genet., 2008, vol. 82, no. 2, pp. 432–443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Voronova, A., Fischer, A., Ryan, T., Al Madhoun, A., and Skerjanc, I.S., PLoS One, 2011, vol. 6, no. 4, p. e19174

  109. Morikawa, Y., Zehir, A., Maska, E., Deng, C., Schneider, M.D., Mishina, Y., and Cserjesi, P., Development, 2009, vol. 136, no. 21, pp. 3575–3584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhang, R., Boareto, M., Engler, A., Louvi, A., Giachino, C., Iber, D., and Taylor, V., Cell Rep., 2019, vol. 28, no. 6, pp. 1485–1498.

    Article  PubMed  CAS  Google Scholar 

  111. Ables, J.L., DeCarolis, N.A., Johnson, M.A., Rivera, P.D., Gao, Z., Cooper, D.C., Radtke, F., Hsieh, J., and Eisch, A.J., J. Neurosci., 2010, vol. 30, no. 31, pp. 10484–10492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nieto-González, J.L., Gómez-Sánchez, L., Mavillard, F., Linares-Clemente, P., Rivero, M.C., Valenzuela-Villatoro, M., Munoz-Bravo, J.L., Pardal, R., and Fernández-Chacón, R., Proc. Natl. Acad. Sci. USA, 2019, vol. 116, no. 16, pp. 8000–8009.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  113. Ji, R., Meng, L., Li, Q., and Lu, Q., Metabolic Brain Dis., 2015, vol. 30, no. 3, pp. 633–644.

    Article  CAS  Google Scholar 

  114. Zelentsova, K., Talmi, Z., Abboud-Jarrous, G., Sapir, T., Capucha, T., Nassar, M., and Burstyn-Cohen, T., Stem Cells, 2017, vol. 35, no. 3, pp. 679–693.

    Article  CAS  PubMed  Google Scholar 

  115. Knobloch, M., Braun, S.M.G., and Zurkirchen, L., Von Schoultz, C., Zamboni, N., Araúzo-Bravo, M.J., Kovacs, W.J., Karalay, Ö., Suter, U., Machado, R.A.C., Roccio, M., Lutolf, M.P., Semenkovich, C.F., and Jessberger, S., Nature, 2013, vol. 493, no. 7431, pp. 226–230.

    Article  CAS  PubMed  Google Scholar 

  116. Adusumilli, V.S., Walker, T.L., Overall, R.W., Klatt, G.M., Zeidan, S.A., Fischer, T.J., Zocher, S., Sykes, A.M., Reinhardt, S., Dahl, A., Kirova, D.G., Mansfeld, J., Rünker, A.E., and Kempermann, G., BioRxiv, 2019, p. 606186.

  117. Huang, E.J. and Reichardt, L.F., Annu. Rev. Neurosci., 2001, vol. 24, no. 1, pp. 677–736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Ceni, C., Unsain, N., Zeinieh, M.P., and Barker, P.A., Handb. Exp. Pharmacol., 2014, vol. 220, pp. 193–221.

    Article  CAS  PubMed  Google Scholar 

  119. Hallböök, F., Curr. Opin. Neurobiol., 1999, vol. 9, no. 5, pp. 616–621.

    Article  PubMed  Google Scholar 

  120. Maisonpierre, P.C., Belluscio, L., Friedman, B., Alderson, R.F., Wiegand, S.J., Furth, M.E., Lindsay, R.M., and Yancopoulos, G.D., Neuron, 1990, vol. 5, no. 4, pp. 501–509.

    Article  CAS  PubMed  Google Scholar 

  121. Nibuya, M., Morinobu, S., and Duman, R.S., J. Neurosci., 1995, vol. 15, no. 11, pp. 7539–7547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Bergami, M., Rimondini, R., Santi, S., Blum, R., Götz, M., and Canossa, M., Proc. Natl. Acad. Sci. USA, 2008, vol. 105, no. 40, pp. 15570–15575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Groves, N., O’Keeffe, I., Lee, W., Toft, A., Blackmore, D., Bandhavkar, S., Coulson, E.J., Bartlett, P.F., and Jhaveri, D.J., Dev. Neurobiol., 2019, vol. 79, nos 9–10, pp. 868–879.

    Article  CAS  PubMed  Google Scholar 

  124. Li, Y., Luikart, B.W., Birnbaum, S., Chen, J., Kwon, C.H., Kernie, S.G., Bassel-Duby, R., and Parada, L.F., Neuron, 2008, vol. 59, no. 3, pp. 399–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Scharfman, H., Goodman, J., Macleod, A., Phani, S., Antonelli, C., and Croll, S., Exp. Neurol., 2005, vol. 192, no. 2, pp. 348–356.

    Article  CAS  PubMed  Google Scholar 

  126. Taliaz, D., Stall, N., Dar, D.E., and Zangen, A., Mol. Psychiatry, 2010, vol. 15, no. 1, pp. 80–92.

    Article  CAS  PubMed  Google Scholar 

  127. Sairanen, M., Lucas, G., Ernfors, P., Castrén, M., and Castren, E., J. Neurosci., 2005, vol. 25, no. 5, pp. 1089–1094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Marvanová, M., Lakso, M., Pirhonen, J., Nawa, H., Wong, G., and Castrén, E., Mol. Cell. Neurosci., 2001, vol. 18, no. 3, pp. 247–258.

    Article  PubMed  CAS  Google Scholar 

  129. Woodbury, M.E. and Ikezu, T., J. Neuroimmune Pharmacol., 2014, vol. 9, no. 2, pp. 92–101.

    Article  PubMed  Google Scholar 

  130. Jin, K., Zhu, Y., Sun, Y., Mao, X.O., Xie, L., and Greenberg, D.A., Proc. Natl. Acad. Sci. USA, 2002, vol. 99, no. 18, pp. 11946–11950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Rai, K.S., Hattiangady, B., and Shetty, A.K., Eur. J. Neurosci., 2007, vol. 26, no. 7, pp. 1765–1779.

    Article  PubMed  Google Scholar 

  132. Bernal, G.M. and Peterson, D.A., Aging Cell, 2011, vol. 10, no. 3, pp. 466–482.

    Article  CAS  PubMed  Google Scholar 

  133. Yang, S.Z., Zhang, L.M., Huang, Y.L., and Sun, F.Y., Anat. Rec. Part A Discov. Mol. Cell. EV, 2003, vol. 274, no. 1, pp. 851–856.

    Google Scholar 

  134. Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., Beccari, S., Huguet, P., Abiega, O., Alberdi, E., Matute, C., Bernales, I., Schulz, A., Otrokocsi, L., Sperlagh, B., Happonen, K.E., Lemke, G., Maletic-Savatic, M., Valero, J., et al., J. Neurosci., 2020, vol. 40, no. 7, pp. 1453–1482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Komiya, Y. and Habas, R., Organogenes, 2008, vol. 4, no. 2, pp. 68–75.

    Article  Google Scholar 

  136. Gordon, M.D. and Nusse, R., J. Biol. Chem., 2006, vol. 281, no. 32, pp. 22429–22433.

    Article  CAS  PubMed  Google Scholar 

  137. Zhang, L., Yang, X., Yang, S., and Zhang, J., Eur. J. Neurosci., 2011, vol. 33, no. 1, pp. 1–8.

    Article  PubMed  Google Scholar 

  138. Varela-Nallar, L. and Inestrosa, N.C., Front. Cell. Neurosci., 2013, vol. 7, no. 100, pp. 1–11.

    Article  CAS  Google Scholar 

  139. Jang, M.H., Bonaguidi, M.A., Kitabatake, Y., Sun, J., Song, J., Kang, E., Jun, H., Zhong, C., Su, Y., Guo, J.U., Wang, M.X., Sailor, K.A., Kim, J.Y., Gao, Y., Christian, K.M., Ming, G.L., and Song, H., Cell Stem Cell, 2013, vol. 12, no. 2, pp. 215–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Seib, D.R.M., Corsini, N.S., Ellwanger, K., Plaas, C., Mateos, A., Pitzer, C., Niehrs, C., Celikel, T., and Martin-Villalba, A., Cell Stem Cell, 2013, vol. 12, no. 2, pp. 204–214.

    Article  CAS  PubMed  Google Scholar 

  141. Gonzalez-Reyes, L.E., Chiang, C.C., Zhang, M., Johnson, J., Arrillaga-Tamez, M., Couturier, N.H., Reddy, N., Starikov, L., Capadona, J.R., Kottmann, A.H., and Durand, D.M., Sci. Rep., 2019, vol. 9, no. 1, p. 17402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Antonelli, F., Casciati, A., and Pazzaglia, S., Neural Regen. Res., 2019, vol. 14, no. 1, pp. 59–61.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Yousef, H., Morgenthaler, A., Schlesinger, C., Bugaj, L., Conboy, I.M., and Schaffer, D.V., Stem Cells, 2015, vol. 33, no. 5, pp. 1577–1588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Lavado, A. and Oliver, G., Dev. Biol., 2014, vol. 388, no. 1, pp. 11–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Stump, G., Durrer, A., Klein, A.-L., Lütolf, S., Suter, U., and Taylor, V., Mech. Dev., 2002, vol. 114, nos. 1–2, pp. 153–159.

    Article  CAS  PubMed  Google Scholar 

  146. Bonaguidi, M.A., Peng, C.Y., McGuire, T., Falciglia, G., Gobeske, K.T., Czeisler, C., and Kessler, J.A., J. Neurosci., 2008, vol. 28, no. 37, pp. 9194–9204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Akita, K., von Holst, A., Furukawa, Y., Mikami, T., Sugahara, K., and Faissner, A., Stem Cells, 2008, vol. 26, no. 3, pp. 798–809.

    Article  CAS  PubMed  Google Scholar 

  148. Sirko, S., Von Holst, A., Wizenmann, A., Götz, M., and Faissner, A., Development, 2007, vol. 134, no. 15, pp. 2727–2738.

    Article  CAS  PubMed  Google Scholar 

  149. Huang, Z., Shimazu, K., Woo, N.H., Zang, K., Müller, U., Lu, B., and Reichardt, L.F., J. Neurosci., 2006, vol. 26, no. 43, pp. 11208–11219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Kokovay, E., Wang, Y., Kusek, G., Wurster, R., Lederman, P., Lowry, N., Shen, Q., and Temple, S., Cell Stem Cell, 2012, vol. 11, no. 2, pp. 220–230.

    Article  CAS  PubMed  Google Scholar 

  151. Porlan, E., Martí-Prado, B., Morante-Redolat, J.M., Consiglio, A., Delgado, A.C., Kypta, R., Löpez-Otín, C., Kirstein, M., and Fariñas, I., Nat. Cell Biol., 2014, vol. 16, no. 7, pp. 629–638.

    Article  CAS  PubMed  Google Scholar 

  152. Barkho, B.Z., Song, H., Aimone, J.B., Smrt, R.D., Kuwabara, T., Nakashima, K., Gage, F.H., and Zhao, X., Stem Cells Dev., 2006, vol. 15, no. 3, pp. 407–421.

    Article  CAS  PubMed  Google Scholar 

  153. Catavero, C., Bao, H., and Song, J., Cell Tissue Res., 2018, vol. 371, no. 1, pp. 33–46.

    Article  CAS  PubMed  Google Scholar 

  154. Bao, H., Asrican, B., Li, W., Gu, B., Wen, Z., Lim, S.A., Haniff, I., Ramakrishnan, C., Deisseroth, K., Philpot, B., and Song, J., Cell Stem Cell, 2017, vol. 21, no. 5, pp. 604–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Klempin, F., Beis, D., Mosienko, V., Kempermann, G., Bader, M., and Alenina, N., J. Neurosci., 2013, vol. 33, no. 19, pp. 8270–8275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dranovsky, A., Picchini, A.M., Moadel, T., Sisti, A.C., Yamada, A., Kimura, S., Leonardo, E.D., and Hen, R., Neuron, 2011, vol. 70, no. 5, pp. 908–923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ge, S., Goh, E.L.K., Sailor, K.A., Kitabatake, Y., Ming, G.L., and Song, H., Nature, 2006, vol. 439, no. 7076, pp. 589–593.

    Article  CAS  PubMed  Google Scholar 

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The reported study was funded by RFBR, project no. 19-115-50079.

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Mal’tsev, D.I., Podgornyi, O.V. Molecular and Cellular Mechanisms Regulating Quiescence and Division of Hippocampal Stem Cells. Neurochem. J. 14, 329–346 (2020). https://doi.org/10.1134/S1819712420040054

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