Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motoneuron loss in the CNS. In G93A-SOD1 mice, motoneuron degeneration is associated with proliferative restorative attempts of ependymal stem progenitor cells (epSPCs), usually quiescent in the spinal cord. The aims of the study were to demonstrate that epSPCs isolated from the spinal cord of G93A-SOD1 mice express neurogenic potential in vitro, and thus gain a better understanding of epSPC neural differentiation properties. For this purpose, we compared the ability of epSPCs from asymptomatic and symptomatic G93A-SOD1 and WT SOD1 transgenic mice to proliferate and differentiate into neural cells. Compared to control cells, G93A-SOD1 epSPCs differentiated more into neurons than into astrocytes, whereas oligodendrocyte proportions were similar in the two populations. G93A-SOD1 neurons were small and astrocytes had an activated phenotype. Evaluation of microRNAs, specific for neural cell fate and cell-cycle regulation, in G93A-SOD1 epSPCs showed that miR-9, miR-124a, miR-19a and miR-19b were differentially expressed. Expression analysis of the predicted miRNA targets allowed identification of a functional network in which Hes1, Pten, Socs1, and Stat3 genes were important for controlling epSPC fate. Our findings demonstrate that G93A-SOD1 epSPCs are a source of multipotent cells that have neurogenic potential in vitro, and might be a useful tool to investigate the mechanisms of neural differentiation in relation to miRNA expression whose modulation might constitute new targeted therapeutic approaches to ALS. © 2013 Elsevier Inc.

Marcuzzo, S., Kapetis, D., Mantegazza, R., Baggi, F., Bonanno, S., Barzago, C., et al. (2014). Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells. EXPERIMENTAL NEUROLOGY, 253, 91-101 [10.1016/j.expneurol.2013.12.007].

Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells

BONANNO, SILVIA;
2014

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motoneuron loss in the CNS. In G93A-SOD1 mice, motoneuron degeneration is associated with proliferative restorative attempts of ependymal stem progenitor cells (epSPCs), usually quiescent in the spinal cord. The aims of the study were to demonstrate that epSPCs isolated from the spinal cord of G93A-SOD1 mice express neurogenic potential in vitro, and thus gain a better understanding of epSPC neural differentiation properties. For this purpose, we compared the ability of epSPCs from asymptomatic and symptomatic G93A-SOD1 and WT SOD1 transgenic mice to proliferate and differentiate into neural cells. Compared to control cells, G93A-SOD1 epSPCs differentiated more into neurons than into astrocytes, whereas oligodendrocyte proportions were similar in the two populations. G93A-SOD1 neurons were small and astrocytes had an activated phenotype. Evaluation of microRNAs, specific for neural cell fate and cell-cycle regulation, in G93A-SOD1 epSPCs showed that miR-9, miR-124a, miR-19a and miR-19b were differentially expressed. Expression analysis of the predicted miRNA targets allowed identification of a functional network in which Hes1, Pten, Socs1, and Stat3 genes were important for controlling epSPC fate. Our findings demonstrate that G93A-SOD1 epSPCs are a source of multipotent cells that have neurogenic potential in vitro, and might be a useful tool to investigate the mechanisms of neural differentiation in relation to miRNA expression whose modulation might constitute new targeted therapeutic approaches to ALS. © 2013 Elsevier Inc.
Articolo in rivista - Articolo scientifico
Amyotrophic lateral sclerosis; Ependymal stem progenitor cell differentiation; Ependymal stem progenitor cells; Functional network; G93A-SOD1 mouse; MicroRNAs; Age Factors; Animals; Cell Differentiation; Cell Proliferation; Ependyma; Gene Expression Regulation; Gene Regulatory Networks; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs; Nerve Tissue Proteins; Neurons; O Antigens; Octamer Transcription Factor-3; Receptors, N-Methyl-D-Aspartate; SOXB1 Transcription Factors; Spinal Cord; Stem Cells; Superoxide Dismutase; Tubulin; Neurology; Developmental Neuroscience
English
2014
253
91
101
none
Marcuzzo, S., Kapetis, D., Mantegazza, R., Baggi, F., Bonanno, S., Barzago, C., et al. (2014). Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells. EXPERIMENTAL NEUROLOGY, 253, 91-101 [10.1016/j.expneurol.2013.12.007].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/132180
Citazioni
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 30
Social impact