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

16 Citations (Scopus)

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

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Neural Stem Cells
Stem cells
Proteins
Endoplasmic Reticulum-Associated Degradation
Multipotent Stem Cells
Nestin
Pluripotent Stem Cells
Oligodendroglia
Embryonic Stem Cells
Astrocytes
Uterus
Embryonic Structures
Maintenance
Neurons
Apoptosis
Modulation
Cell Self Renewal
Derivatives
Degradation
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

mSEL-1L (suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment. / Cardano, Marina; Diaferia, Giuseppe R.; Cattaneo, Monica; Dessì, Sara S.; Long, Qiaoming; Conti, Luciano; DeBlasio, Pasquale; Cattaneo, Elena; Biunno, Ida.

In: Journal of Biological Chemistry, Vol. 286, No. 21, 27.05.2011, p. 18708-18719.

Research output: Contribution to journalArticle

Cardano, Marina ; Diaferia, Giuseppe R. ; Cattaneo, Monica ; Dessì, Sara S. ; Long, Qiaoming ; Conti, Luciano ; DeBlasio, Pasquale ; Cattaneo, Elena ; Biunno, Ida. / mSEL-1L (suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 21. pp. 18708-18719.
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