STEM CELL PLASTICITY IN ADULT NEUROGENIC NICHES

Introduction

Somatic stem cells (SCs) sustain tissue renewal and regeneration in adult mammals. The maintenance of their stemness and long-lasting preservation in cohabitation with differentiated progeny at specific niches poses these cells to a considerable challenge.

Cellular Plasticity

To deal with it, SCs display a complex network of yet to be fully uncovered mechanisms that allow multilevel plasticity. Cellular plasticity indicates the ability of cells to reversibly change their phenotype in response to the microenvironment.

Neural Stem Cells

In the subependymal zone of the adult rodent brain, self-renewing neural SCs (NSCs) generate new neurons for pre-existing olfactory circuits. It is clear that NSCs must be endowed with plasticity properties, but the analysis of these potential traits needs a precise definition and a combination of comprehensive approaches to unravel their molecular regulation.

Research Objectives

Building from our new technologies and some preliminary data, in this proposal we will try to advance in the molecular basis and extent of the cell plasticity repertoire of adult subependymal NSCs by concentrating on three of its potential forms:

1. Epithelial plasticity: The ability to dynamically and reversibly undergo epithelial-to-mesenchymal transitions, a form of cell adaptation that has never been conceptually proposed or evaluated in adult NSCs.

2. Cycling plasticity: The ability to move in and out of the cell cycle and remain quiescent for long periods of time. This plasticity clearly exists, but its molecular regulation remains largely elusive.

3. Immune plasticity: The capacity to evade adaptive immunity. Our view about immunity in the brain has dramatically changed in the last few years, raising interest in its potential interaction with NSCs.

Implications

Understanding cell plasticity traits in NSCs may contribute to understanding not only NSC and/or SC behavior but also glioma biology and to identify pathways to intervene in brain tumor treatment.