A perturbed MicroRNA expression pattern characterizes embryonic neural stem cells derived from a severe mouse model of spinal muscular atrophy (SMA)

Andrea Luchetti, Silvia Anna Ciafrè, Michela Murdocca, Arianna Malgieri, Andrea Masotti, Massimo Sanchez, Maria Giulia Farace, Giuseppe Novelli, Federica Sangiuolo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)18312-18327
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 6 2015

Keywords

  • microRNAs (miRNAs)
  • Motor neurons (MNs)
  • Neural stem cells (NSCs)
  • Spinal muscular atrophy (SMA)
  • Survival motor neuron (SMN)

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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