mSEL-1L (suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment

Marina Cardano, Giuseppe R. Diaferia, Monica Cattaneo, Sara S. Dessì, Qiaoming Long, Luciano Conti, Pasquale DeBlasio, Elena Cattaneo, Ida Biunno

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)18708-18719
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number21
DOIs
Publication statusPublished - May 27 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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