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The Stem Cell Factor Sox2 Is a Positive Timer of Oligodendrocyte Development in the Postnatal Murine Spinal Cord

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Abstract

Myelination in the central nervous system takes place predominantly during the postnatal development of humans and rodents by myelinating oligodendrocytes (OLs), which are differentiated from oligodendrocyte progenitor cells (OPCs). We recently reported that Sox2 is essential for developmental myelination in the murine brain and spinal cord. It is still controversial regarding the role of Sox2 in oligodendroglial lineage progression in the postnatal murine spinal cord. Analyses of a series of cell- and stage-specific Sox2 mutants reveal that Sox2 plays a biphasic role in regulating oligodendroglial lineage progression in the postnatal murine spinal cord. Sox2 controls the number of OPCs for subsequent differentiation through regulating their proliferation. In addition, Sox2 regulates the timing of OL differentiation and modulates the rate of oligodendrogenesis. Our experimental data prove that Sox2 is an intrinsic positive timer of oligodendroglial lineage progression and suggest that interventions affecting oligodendroglial Sox2 expression may be therapeutic for overcoming OPC differentiation arrest in dysmyelinating and demyelinating disorders.

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References

  1. Franklin RJ, Gallo V (2014) The translational biology of remyelination: past, present, and future. Glia 62:1905–1915

    Article  Google Scholar 

  2. Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39(5):749–765

    Article  CAS  Google Scholar 

  3. Lee KE, Seo J, Shin J, Ji EH, Roh J, Kim JY, Sun W, Muhr J et al (2014) Positive feedback loop between Sox2 and Sox6 inhibits neuronal differentiation in the developing central nervous system. Proc Natl Acad Sci U S A 111(7):2794–2799

    Article  CAS  Google Scholar 

  4. Kondo T, Raff M (2004) Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells. Genes Dev 18(23):2963–2972

    Article  CAS  Google Scholar 

  5. Lyssiotis CA, Walker J, Wu C, Kondo T, Schultz PG, Wu X (2007) Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells. Proc Natl Acad Sci U S A 104(38):14982–14987

    Article  CAS  Google Scholar 

  6. Niu W, Zang T, Zou Y, Fang S, Smith DK, Bachoo R, Zhang CL (2013) In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat Cell Biol 15(10):1164–1175

    Article  CAS  Google Scholar 

  7. Su Z et al (2014) In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun 5:3338

    Article  Google Scholar 

  8. Heinrich C, Bergami M, Gascón S, Lepier A, Viganò F, Dimou L, Sutor B, Berninger B et al (2014) Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Reports 3(6):1000–1014

    Article  CAS  Google Scholar 

  9. Hoffmann SA, Hos D, Kuspert M, Lang RA, Lovell-Badge R, Wegner M, Reiprich S (2014) Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes. Development 141(1):39–50

    Article  CAS  Google Scholar 

  10. Zhao C, Ma D, Zawadzka M, Fancy SPJ, Elis-Williams L, Bouvier G, Stockley JH, de Castro GM et al (2015) Sox2 sustains recruitment of oligodendrocyte progenitor cells following CNS demyelination and primes them for differentiation during remyelination. J Neurosci 35(33):11482–11499

    Article  CAS  Google Scholar 

  11. Zhang S, Zhu X, Gui X, Croteau C, Song L, Xu J, Wang A, Bannerman P et al (2018) Sox2 is essential for oligodendroglial proliferation and differentiation during postnatal brain myelination and CNS remyelination. J Neurosci 38:1802–1820

    Article  CAS  Google Scholar 

  12. Stolt CC, Rehberg S, Ader M, Lommes P, Riethmacher D, Schachner M, Bartsch U, Wegner M (2002) Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev 16(2):165–170

    Article  CAS  Google Scholar 

  13. Hammond E, Lang J, Maeda Y, Pleasure D, Angus-Hill M, Xu J, Horiuchi M, Deng W et al (2015) The Wnt effector transcription factor 7-like 2 positively regulates oligodendrocyte differentiation in a manner independent of Wnt/beta-catenin signaling. J Neurosci 35(12):5007–5022

    Article  Google Scholar 

  14. Lang J, Maeda Y, Bannerman P, Xu J, Horiuchi M, Pleasure D, Guo F (2013) Adenomatous polyposis coli regulates oligodendroglial development. J Neurosci: Off J Soc Neurosci 33(7):3113–3130

    Article  CAS  Google Scholar 

  15. Zhao C, Deng Y, Liu L, Yu K, Zhang L, Wang H, He X, Wang J et al (2016) Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation. Nat Commun 7:10883

    Article  CAS  Google Scholar 

  16. Dugas JC, Cuellar TL, Scholze A, Ason B, Ibrahim A, Emery B, Zamanian JL, Foo LC et al (2010) Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron 65(5):597–611

    Article  CAS  Google Scholar 

  17. Moyon S, Huynh JL, Dutta D, Zhang F, Ma D, Yoo S, Lawrence R, Wegner M et al (2016) Functional characterization of DNA methylation in the oligodendrocyte lineage. Cell Rep 15:748–760

    Article  CAS  Google Scholar 

  18. Moyon S, Casaccia P (2017) DNA methylation in oligodendroglial cells during developmental myelination and in disease. Neurogenesis (Austin) 4(1):e1270381

    Article  Google Scholar 

  19. Ishii A, Fyffe-Maricich SL, Furusho M, Miller RH, Bansal R (2012) ERK1/ERK2 MAPK signaling is required to increase myelin thickness independent of oligodendrocyte differentiation and initiation of myelination. J Neurosci 32(26):8855–8864

    Article  CAS  Google Scholar 

  20. Ishii A, Furusho M, Bansal R (2013) Sustained activation of ERK1/2 MAPK in oligodendrocytes and Schwann cells enhances myelin growth and stimulates oligodendrocyte progenitor expansion. J Neurosci 33(1):175–186

    Article  CAS  Google Scholar 

  21. Marques S, Zeisel A, Codeluppi S, van Bruggen D, Mendanha Falcao A, Xiao L, Li H, Haring M et al (2016) Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 352(6291):1326–1329

    Article  CAS  Google Scholar 

  22. Dai J, Bercury KK, Ahrendsen JT, Macklin WB (2015) Olig1 function is required for oligodendrocyte differentiation in the mouse brain. J Neurosci 35(10):4386–4402

    Article  CAS  Google Scholar 

  23. Shen S, Sandoval J, Swiss VA, Li J, Dupree J, Franklin RJM, Casaccia-Bonnefil P (2008) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci 11(9):1024–1034

    Article  CAS  Google Scholar 

  24. Fernandez-Castaneda A, Gaultier A (2016) Adult oligodendrocyte progenitor cells—multifaceted regulators of the CNS in health and disease. Brain Behav Immun 57:1–7

    Article  CAS  Google Scholar 

  25. Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron 77(5):873–885

    Article  CAS  Google Scholar 

  26. Xiao L, Ohayon D, McKenzie IA, Sinclair-Wilson A, Wright JL, Fudge AD, Emery B, Li H et al (2016) Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning. Nat Neurosci 19(9):1210–1217

    Article  CAS  Google Scholar 

  27. Tripathi RB, Jackiewicz M, McKenzie IA, Kougioumtzidou E, Grist M, Richardson WD (2017) Remarkable stability of myelinating oligodendrocytes in mice. Cell Rep 21(2):316–323

    Article  CAS  Google Scholar 

  28. Reiprich S, Wegner M (2014) From CNS stem cells to neurons and glia: Sox for everyone. Cell Tissue Res

  29. Reiprich S, Wegner M (2014) Sox2: a multitasking networker. Neurogenesis (Austin) 1(1):e962391

    Article  Google Scholar 

  30. Liu YR, Laghari ZA, Novoa CA, Hughes J, Webster JRM, Goodwin PE, Wheatley SP, Scotting PJ (2014) Sox2 acts as a transcriptional repressor in neural stem cells. BMC Neurosci 15:95

    Article  Google Scholar 

  31. Engelen E, Akinci U, Bryne JC, Hou J, Gontan C, Moen M, Szumska D, Kockx C et al (2011) Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Nat Genet 43(6):607–611

    Article  CAS  Google Scholar 

  32. Jung M, Krämer E, Grzenkowski M, Tang K, Blakemore W, Aguzzi A, Khazaie K, Chlichlia K et al (1995) Lines of murine oligodendroglial precursor cells immortalized by an activated neu tyrosine kinase show distinct degrees of interaction with axons in vitro and in vivo. Eur J Neurosci 7(6):1245–1265

    Article  CAS  Google Scholar 

  33. He Y, Dupree J, Wang J, Sandoval J, Li J, Liu H, Shi Y, Nave KA et al (2007) The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 55(2):217–230

    Article  CAS  Google Scholar 

  34. Ye F, Chen Y, Hoang TN, Montgomery RL, Zhao XH, Bu H, Hu T, Taketo MM et al (2009) HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci 12(7):829–838

    Article  CAS  Google Scholar 

  35. Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH (2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109(1):75–86

    Article  CAS  Google Scholar 

  36. Chen C et al (2017) Astrocyte-specific deletion of Sox2 promotes functional recovery after traumatic brain injury. Cereb Cortex:1–16

  37. Wheeler NA, Fuss B (2016) Extracellular cues influencing oligodendrocyte differentiation and (re)myelination. Exp Neurol 283(Pt B):512–530

    Article  CAS  Google Scholar 

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Acknowledgements

Grant support was from Shriners Hospitals for Children (F.G., S.Z.), 2016YFC0503200 (X. Z.), and NIH (R01NS094559, R21NS093559 to F.G.).

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Authors and Affiliations

  1. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children/UC Davis School of Medicine, Sacramento, CA, 95817, USA

    Sheng Zhang, Abeer Rasai, Yan Wang, Jie Xu, Peter Bannerman, Daffcar Erol, Danayit Tsegaye, Aijun Wang, Athena Soulika & Fuzheng Guo

  2. Department of Neurology, School of Medicine, UC Davis, Davis, CA, 95817, USA

    Sheng Zhang, Yan Wang & Fuzheng Guo

  3. Department of Cell Biology and Human Anatomy, School of Medicine, UC Davis, Davis, CA, 95817, USA

    Peter Bannerman

  4. Department of Surgery, School of Medicine, UC Davis, Davis, CA, 95817, USA

    Aijun Wang

  5. Department of Dermatology, School of Medicine, UC Davis, Davis, CA, 95817, USA

    Athena Soulika

  6. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China

    Xiangjiang Zhan

  7. Department of Neurology, UC Davis School of Medicine, c/o Shriners Hospitals for Children, Room 601A, 2425 Stockton Blvd, Sacramento, CA, 95817, USA

    Fuzheng Guo

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  1. Sheng Zhang
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Correspondence to Fuzheng Guo.

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Zhang, S., Rasai, A., Wang, Y. et al. The Stem Cell Factor Sox2 Is a Positive Timer of Oligodendrocyte Development in the Postnatal Murine Spinal Cord. Mol Neurobiol 55, 9001–9015 (2018). https://doi.org/10.1007/s12035-018-1035-7

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  • DOI: https://doi.org/10.1007/s12035-018-1035-7

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