Protein s negatively regulates neural stem cell self-renewal through bmi-1 signaling

Katya Zelentsova-Levytskyi, Ziv Talmi, Ghada Abboud-Jarrous, Tal Capucha, Tamar Sapir, Tal Burstyn-Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 Pros1 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 downstreameffectors p16Ink4a and p19Arf to promote NSPC self-renewal in Pros1-ablated cells. Rescuing Pros1 expression restores normal levels of Bmi-1 signaling, and reverts the proliferation and enhanced self-renewal phenotypes observed in Pros1-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.

Original languageAmerican English
Article number124
JournalFrontiers in Molecular Neuroscience
StatePublished - 2 May 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Zelentsova-Levytskyi, Talmi, Abboud-Jarrous, Capucha, Sapir and Burstyn-Cohen. This is an open-access article distributed under the terms


  • Bmi-1
  • Neural stem cells
  • Neurogenesis
  • PROS1
  • Protein S
  • Self-renewal

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