A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)

International Journal of Molecular Sciences

Andrea Luchetti¹  Silvia Anna Ciafrè¹  Michela Murdocca¹  Arianna Malgieri¹  Andrea Masotti²  Massimo Sanchez³  Maria Giulia Farace¹  Giuseppe Novelli¹  Federica Sangiuolo¹ 

[1] Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; E-Mails:;Gene Expression-Microarrays Laboratory, Bambino Gesù Children’s Hospital-IRCCS Polo di Ricerca-V.le di San Paolo 15, 00146 Rome, Italy; E-Mail:;Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy; E-Mail:

关键词: survival motor neuron (SMN);    spinal muscular atrophy (SMA);    neural stem cells (NSCs);    motor neurons (MNs);    microRNAs (miRNAs);   

DOI  :  10.3390/ijms160818312

来源: mdpi

【 摘 要 】

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.