Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications.

Amber Penning,Pascal Bielefeld,Evgenia Salta,Davide De Pietri Tonelli,Carlos P Fitzsimons,Oihane Abiega,Giorgia Tosoni,Caterina Gasperini

doi:10.3389/fncel.2021.781434

Abstract

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases.

Highlights

After birth, most of the mammalian brain presents a cellular environment that is refractory to the generation of new neurons under physiological conditions (Kempermann, 2015)
We focus on regulatory small non-coding RNAs (sncRNAs) (Figure 2), and in particular on microRNAs, which are the most studied sncRNA subclass with well-documented and emerging roles in the regulation of adult neural stem cells (aNSCs) and their progeny
The complexity of the biological processes involved in aNSC homeostasis, including activation, self-renewal, and fate determination, requires tight control of numerous multilayered regulatory programs

Summary

Introduction

Most of the mammalian brain presents a cellular environment that is refractory to the generation of new neurons under physiological conditions (Kempermann, 2015). Understanding the regulation of aNSCs and their crosstalk with other cell types within the hippocampal neurogenic niche is indispensable to fully map the mechanisms governing their fate determination under physiological conditions and in the diseased brain.

Results

Conclusion