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