Stem Cells. 2021 Aug 16.
Nucleoporins (Nups) are components of the nuclear pore complex that, besides regulating nucleus-cytoplasmic transport, emerged as a hub for chromatin interaction and gene expression modulation. Specifically, Nups act in a dynamic manner both at specific gene level and in the topological organization of chromatin domains. As such, they play a fundamental role during development and determination of stemness/differentiation balance in stem cells. An increasing number of reports indicate the implication of Nups in many central nervous system functions with great impact on neurogenesis, neurophysiology and neurological disorders. Nevertheless, the role of Nup-mediated epigenetic regulation in embryonic and adult neural stem cells (NSCs) is a field largely unexplored and the comprehension of their mechanisms of action is only beginning to be unveiled. After a brief overview of epigenetic mechanisms, we will present and discuss the emerging role of Nups as new effectors of neuroepigenetics and as dynamic platform for chromatin function with specific reference to the biology of NSCs. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Adult neurogenesis supports brain function by providing new neurons for tissue homeostasis and memory processes. Unfortunately, decreased neurogenesis occurs during aging and in neurodegenerative diseases, thus reducing brain repair capacity. Greater understanding of the mechanisms implicated in neural stem cell biology could lead to increasing the regenerative potential of these cells for many therapeutic purposes. This paper reviews the emerging role of nuclear pore proteins as novel key molecules that, by epigenetic mechanisms, control stemness and fate specification of neural progenitors in the developing embryo and in the adult brain.
Keywords: Alzheimer's disease; epigenetics; neural stem cells; neurogenesis; nucleoporins