Protein S Negatively Regulates Neural Stem Cell Self-Renewal through Bmi-1 Signaling

Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expressi...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2017-05, Vol.10, p.124-124
Main Authors: Zelentsova-Levytskyi, Katya, Talmi, Ziv, Abboud-Jarrous, Ghada, Capucha, Tal, Sapir, Tamar, Burstyn-Cohen, Tal
Format: Article
Language:English
Subjects:
Apoptosis
Bmi protein
Bmi-1
Cell cycle
Cell proliferation
Cell self-renewal
Embryo cells
Hippocampus
Homeostasis
INK4a protein
Ligands
Molecular modelling
Nervous system
Neural stem cells
Neurogenesis
Neuroscience
p16 Protein
Phenotypes
Polycomb group proteins
Progenitor cells
PROS1
Protein S
Proteins
self-renewal
Stem cells
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Summary:Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expression of Protein S (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC quiescence and neuronal differentiation. Here, we investigate the effect of PROS1 on NSPC self-renewal and show that genetic ablation of in neural progenitors increased NSPC self-renewal by 50%. Mechanistically, we identified the upregulation of the polycomb complex protein Bmi-1 and repression of its downstream effectors p16 and p19 to promote NSPC self-renewal in -ablated cells. Rescuing expression restores normal levels of Bmi-1 signaling, and reverts the proliferation and enhanced self-renewal phenotypes observed in -deleted cells. Our study identifies PROS1 as a novel negative regulator of NSPC self-renewal. We conclude PROS1 is instructive for NSPC differentiation by negatively regulating Bmi-1 signaling in adult and embryonic neural stem cells.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2017.00124