You are here


Dual Roles for Pros1 Expression in Adult Neural Stem Cells

Review of “Protein S Regulates Neural Stem Cell Quiescence and Neurogenesis” from Stem Cells by Stuart P. Atkinson

Neurogenesis in the subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ) [1] of the adult mammalian brain requires the controlled activation, proliferation, and differentiation of previously quiescent adult neural stem cells (NSCs). However, what are the controlling mechanisms underlying adult neurogenesis and how are these mechanisms regulated? 

A new Stem Cells study from the laboratory of Tal Burstyn-Cohen (Hebrew University-Hadassah, Jerusalem, Israel) now demonstrates that Protein S (Pros1), known for its potent blood anticoagulant activity [2], plays an important dual role in the regulation of adult neural stem cell quiescence/proliferation and in daughter cell fate determination [3].

Initial immunohistochemical analyses confirmed the presence of Pros1 expression in the quiescent NSCs of the adult mouse hippocampus. However, deletion of Pros1 forced NSCs to exit quiescence and proliferate due to a reduction in Notch1-mediated signaling. Proliferative Pros1-KO NSCs maintained their multilineage differentiation potential, although the rate of neurogenesis decreased at the same rate at astrogenesis increased, suggesting another role for Pros1, this time in controlling NSC fate. Interestingly, treatment of Pros1-KO NSCs with medium conditioned by wild-type NSCs or exogenous purified Pros1 protein rescued Pros1-KO phenotypes suggesting that Pros1 secretion by NSCs functions by an NSC-endogenous mechanism.

Overall, the study proposes that Pros1 plays novel roles in the homeostatic regulation of adult neural stem cells via Notch1 signaling and the promotion of neurogenesis over astrocytosis. This invaluable information may prove important to future exogenous and endogenous neural stem cell-based therapies, the deeper understanding of many diseases and disorders of the brain, and may give pause to the application of anticoagulant therapy based on vitamin-K blockers that also target Pros1.


  1. Ming GL and Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011;70:687-702.
  2. ten Kate MK and van der Meer J. Protein S deficiency: a clinical perspective. Haemophilia 2008;14:1222-1228.
  3. Zelentsova K, Talmi Z, Abboud-Jarrous G, et al. Protein S Regulates Neural Stem Cell Quiescence and Neurogenesis. Stem Cells 2017;35:679-693.