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 mmu-miR-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, Differentiation / genetics
-
Antigens, Differentiation / metabolism*
-
Apoptosis / physiology*
-
Astrocytes / cytology
-
Astrocytes / metabolism
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Basic Helix-Loop-Helix Transcription Factors / metabolism
-
Cell Line
-
Cell Lineage / physiology*
-
Eye Proteins / genetics
-
Eye Proteins / metabolism
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism
-
Intermediate Filament Proteins / genetics
-
Intermediate Filament Proteins / metabolism
-
Intracellular Signaling Peptides and Proteins
-
Mice
-
Mice, Transgenic
-
MicroRNAs / genetics
-
MicroRNAs / metabolism
-
Multipotent Stem Cells / cytology
-
Multipotent Stem Cells / metabolism*
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism
-
Nestin
-
Neural Stem Cells / cytology
-
Neural Stem Cells / metabolism*
-
Oligodendrocyte Transcription Factor 2
-
PAX6 Transcription Factor
-
Paired Box Transcription Factors / genetics
-
Paired Box Transcription Factors / metabolism
-
Proteins / genetics
-
Proteins / metabolism*
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
Substances
-
Antigens, Differentiation
-
Basic Helix-Loop-Helix Transcription Factors
-
Eye Proteins
-
Hes5 protein, mouse
-
Homeodomain Proteins
-
Intermediate Filament Proteins
-
Intracellular Signaling Peptides and Proteins
-
MicroRNAs
-
Mirn183 microRNA, mouse
-
Nerve Tissue Proteins
-
Nes protein, mouse
-
Nestin
-
Olig2 protein, mouse
-
Oligodendrocyte Transcription Factor 2
-
PAX6 Transcription Factor
-
Paired Box Transcription Factors
-
Pax6 protein, mouse
-
Proteins
-
Repressor Proteins
-
Sel1h protein, mouse