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Increased Neuronal Differentiation of Neural Progenitor Cells Derived from Phosphovimentin-Deficient Mice.

Journal article
Authors Meng Chen
Till B. Puschmann
Pavel Marasek
Masaki Inagaki
Marcela Pekna
Ulrika Wilhelmsson
Milos Pekny
Published in Molecular neurobiology
Volume 55
Issue 7
Pages 5478–5489
ISSN 1559-1182
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 5478–5489
Language en
Links dx.doi.org/10.1007/s12035-017-0759-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurobiology, Neuroscience

Abstract

Vimentin is an intermediate filament (also known as nanofilament) protein expressed in several cell types of the central nervous system, including astrocytes and neural stem/progenitor cells. Mutation of the vimentin serine sites that are phosphorylated during mitosis (VIMSA/SA) leads to cytokinetic failures in fibroblasts and lens epithelial cells, resulting in chromosomal instability and increased expression of cell senescence markers. In this study, we investigated morphology, proliferative capacity, and motility of VIMSA/SAastrocytes, and their effect on the differentiation of neural stem/progenitor cells. VIMSA/SAastrocytes expressed less vimentin and more GFAP but showed a well-developed intermediate filament network, exhibited normal cell morphology, proliferation, and motility in an in vitro wound closing assay. Interestingly, we found a two- to fourfold increased neuronal differentiation of VIMSA/SAneurosphere cells, both in a standard 2D and in Bioactive3D cell culture systems, and determined that this effect was neurosphere cell autonomous and not dependent on cocultured astrocytes. Using BrdU in vivo labeling to assess neural stem/progenitor cell proliferation and differentiation in the hippocampus of adult mice, one of the two major adult neurogenic regions, we found a modest increase (by 8%) in the fraction of newly born and surviving neurons. Thus, mutation of the serine sites phosphorylated in vimentin during mitosis alters intermediate filament protein expression but has no effect on astrocyte morphology or proliferation, and leads to increased neuronal differentiation of neural progenitor cells.

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