Evidence for a subventricular zone neural stem cell phagocytic activity stimulated by the vitamin K-dependent factor protein S
Autor: | Aurore Gely-Pernot, Aurélie Ginisty, Valérie Coronas, Patricia Arnault, Loubna Abaamrane, Franck Morel, Omar Benzakour |
---|---|
Přispěvatelé: | Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
MESH: Signal Transduction
MESH: Neural Stem Cells animal diseases [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Subventricular zone [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Protein S Mice SOX2 Neural Stem Cells Phagocytosis Lateral Ventricles Proto-Oncogene Proteins [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] medicine Animals MESH: Animals Efferocytosis MESH: Phagocytosis MESH: Mice Tissue homeostasis Cells Cultured MESH: Lateral Ventricles c-Mer Tyrosine Kinase Receptor Protein-Tyrosine Kinases Cell Biology Nestin MERTK Antigens Differentiation Neural stem cell Cell biology MESH: Protein S MESH: Proto-Oncogene Proteins medicine.anatomical_structure Neuropoiesis nervous system MESH: Antigens Differentiation Molecular Medicine MESH: Receptor Protein-Tyrosine Kinases Developmental Biology Signal Transduction MESH: Cells Cultured |
Zdroj: | STEM CELLS STEM CELLS, AlphaMed Press, 2015, 33 (2), pp.515-25. ⟨10.1002/stem.1862⟩ |
ISSN: | 1066-5099 |
DOI: | 10.1002/stem.1862⟩ |
Popis: | Neural stem cells, whose major reservoir in the adult mammalian brain is the subventricular zone (SVZ), ensure neuropoiesis, a process during which many generated cells die. Removal of dead cells and debris by phagocytes is necessary for tissue homeostasis. Using confocal and electron microscopy, we demonstrate that cultured SVZ cells phagocytose both 1 and 2 µm latex beads and apoptotic cell-derived fragments. We determine by flow cytometry that phagocytic cells represent more than 10% of SVZ cultured cells. Phenotyping of SVZ cells using nestin, GFAP, Sox2, or LeX/SSEA and quantification of aldehyde dehydrogenase (ALDH) activity, reveals that cells with neural stem-cell features phagocytose and represent more than 30% of SVZ phagocytic cells. In vivo, nestin-, Sox2-, and ALDH-expressing neural stem-like cells engulfed latex beads or apoptotic cell-derived fragments that were injected into mice lateral brain ventricles. We show also that SVZ cell phagocytic activity is an active process, which depends both on cytoskeleton dynamic and on recognition of phosphatidylserine eat-me signal, and is stimulated by the vitamin K-dependent factor protein S (ProS). ProS neutralizing antibodies inhibit SVZ cell phagocytic activity and exposure of SVZ cells to apoptotic cell-derived fragments induces a transient Mer tyrosine kinase receptor (MerTK) phosphorylation. Conversely, MerTK blocking antibodies impair both basal and ProS-stimulated SVZ cell phagocytic activity. By revealing that neural stem-like cells act within the SVZ neurogenic niche as phagocytes and that the ProS/MerTK path represents an endogenous regulatory mechanism for SVZ cell phagocytic activity, the present report opens-up new perspectives for both stem cell biology and brain physiopathology. Stem Cells 2015;33:515–525 |
Databáze: | OpenAIRE |
Externí odkaz: |