Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmumiR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L / NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L / NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination.
mSEL-1L (suppressor/enhancer LIN12 like) levels influence murine neural stem cell self-renewal and lineage commitment / M. Cardano, G. Diaferia, M. Cattaneo, S.S. Dessì, Q. Long, L. Conti, P. DeBlasio, E. Cattaneo, I. Biunno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 286:21(2011 May 27), pp. 18708-18719.
|Titolo:||mSEL-1L (suppressor/enhancer LIN12 like) levels influence murine neural stem cell self-renewal and lineage commitment|
CARDANO, MARINA (Primo)
DIAFERIA, GIUSEPPE (Secondo)
CATTANEO, ELENA (Penultimo)
|Parole Chiave:||neural stem cells ; differentiation ; mmu-miR-183|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||27-mag-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M110.210740|
|Appare nelle tipologie:||01 - Articolo su periodico|