Murine SEL-1L (mSEL-1L) belongs to the Unfolded Protein Response (UPR) gene family, acting as a “gate keeper” in the control of newly synthesized soluble and membrane proteins. It is essential during mouse development since homozygous mSEL-1L deficient mice are embryonic lethal due to growth impairment with the brain being the most affect region. In the study here presented, we explore the role of this protein in stemness maintenance, analyzing its contribution in Neural Stem Cells (NSCs) self-renewal. We demonstrate that mSEL-1L expression is associated with pluripotency and multipotency states, but is lost during NSCs terminal differentiation into astrocytes, oligodendrocytes and neurons. Interestingly, the protein silencing is partially mediated by the refined post-transcriptional regulation of mmu-miR-183. Our studies support the hypothesis that mSEL-1L protein is responsible of self-renewal control, since its deprivation in NSCs determines in vitro a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2 and a severe proliferation defect. This might be due to an alteration of the Notch pathway, as revealed by the drastic reduction of its effector HES-5. Furthermore, these cells exhibit a premature differentiation tendency, showing high levels of the pro-neural factor Neurogenin 2 and of both the astrocytic and neuronal markers GFAP andIII Tubulin, while the principal NSC stemness makers Nestin and SOX-2 are strongly down-modulated. In conclusion, we propose that the lack mSEL-1L is responsible of the progressive progenitor pool depletion, which ultimately leads to NSC death likely due to the misregulating of the Notch signalling.
SEL-1L influences self-renewal in neural stem cells / M. Cardano, G. Diaferia, M. Cattaneo, S.S. Dessì, Q. Long, L. Conti, P. De Blasio, E. Cattaneo, I. Biunno. ((Intervento presentato al 23. convegno Biennial Meeting of ISN-ESN tenutosi a Atene nel 2011.
|Titolo:||SEL-1L influences self-renewal in neural stem cells|
DIAFERIA, GIUSEPPE (Secondo)
CATTANEO, ELENA (Penultimo)
|Data di pubblicazione:||ago-2011|
|Parole Chiave:||neural stem cells ; development ; differentiation|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Enti collegati al convegno:||International Society for Neurochemistry (ISN)|
European Society for Neurochemistry (ESN)
|Citazione:||SEL-1L influences self-renewal in neural stem cells / M. Cardano, G. Diaferia, M. Cattaneo, S.S. Dessì, Q. Long, L. Conti, P. De Blasio, E. Cattaneo, I. Biunno. ((Intervento presentato al 23. convegno Biennial Meeting of ISN-ESN tenutosi a Atene nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|