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

• Published in: Experimental neurology Vol. 253; pp. 91 - 101
• Main Authors: Marcuzzo, Stefania, Kapetis, Dimos, Mantegazza, Renato, Baggi, Fulvio, Bonanno, Silvia, Barzago, Claudia, Cavalcante, Paola, Kerlero de Rosbo, Nicole, Bernasconi, Pia
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2014; Elsevier
• Subjects: Age Factors; Amyotrophic lateral sclerosis; Animals; Biological and medical sciences; Cell Differentiation - genetics; Cell Proliferation; Cerebrospinal fluid. Meninges. Spinal cord; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Ependyma - cytology; Ependymal stem progenitor cell differentiation; Ependymal stem progenitor cells; Functional network; Fundamental and applied biological sciences. Psychology; G93A-SOD1 mouse; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Gene Regulatory Networks - genetics; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Nerve Tissue Proteins - metabolism; Nervous system (semeiology, syndromes); Neurology; Neurons - metabolism; O Antigens - metabolism; Octamer Transcription Factor-3 - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; SOXB1 Transcription Factors - metabolism; Spinal Cord - anatomy & histology; Stem Cells - metabolism; Stem Cells - physiology; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Tubulin - metabolism; Vertebrates: nervous system and sense organs; Socs1; Dlx2; Nr2e1; Stmn1; Ependymal stem progenitor cell differentiation; ALS; Sox2; NMDA; Hes1; miRNA; Sox9; Oct-4; Ccnd2; FALS; Jag1; Amyotrophic lateral sclerosis; Pten; GAD 67; GFAP; SOD1; epSPCs; SALS; MicroRNAs; Stat3; G93A-SOD1 mouse; Ependymal stem progenitor cells; Functional network; Nervous system diseases; Stem cell; Rodentia; Cell differentiation; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Degenerative disease; Spinal cord disease; Progenitor cell
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2013.12.007

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. •G93A-SOD1 spinal cord is a source of ependymal stem progenitor cells (epSPCs).•epSPCs from G93A-SOD1 mice are multipotent and present neural alterations.•miR-9, miR-124a, miR-19a and miR-19b are altered in G93A-SOD1 epSPCs.•Hes1, Pten, Socs1, Stat3 mRNAs, targets of the analyzed miRNAs, are down-regulated in G93A-SOD1 epSPCs.•epSPCs may constitute a future therapeutic target for ALS.