title: mSEL-1L (Suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment.
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.
authors: Doctorate School of Molecular Medicine, Università degli Studi di Milano, 20100 Milan, Italy.
authors: Marina
authors: M
authors: Cardano
authors: Giuseppe R
authors: GR
authors: Diaferia
authors: Monica
authors: M
authors: Cattaneo
authors: Sara S
authors: SS
authors: Dessì
authors: Qiaoming
authors: Q
authors: Long
authors: Luciano
authors: L
authors: Conti
authors: Pasquale
authors: P
authors: Deblasio
authors: Elena
authors: E
authors: Cattaneo
authors: Ida
authors: I
authors: Biunno
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D064231:Nestin; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D012097:Repressor Proteins; C489685:Hes5 protein, mouse; C543802:Mirn183 microRNA, mouse; C577485:Nes protein, mouse; C512773:Olig2 protein, mouse; C000605732:Pax6 protein, mouse; C492169:Sel1h protein, mouse