MicroRNA Profiling Reveals Unique miRNA Signatures in IGF-1 Treated Embryonic Striatal Stem Cell Fate Decisions in Striatal NeurogenesisIn Vitro

Abstract

The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF + bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications.

Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications

“…Additionally, down-regulation of miR-433 expression has been observed in children with autism [ 87 ]. Considering the putative role of miR-433 in striatal neurogenesis [ 88 ], the current findings in the transgenic MSA model and its relevance to the findings in the human disease strengthen the possible role of this specific candidate in the early stages of MSA neurodegeneration. Furthermore, miR-433 is involved in the regulation of HDAC6 expression [ 89 ; 90 ] that has been shown to co-localize with α-synuclein in GCIs in the MSA brain [ 91 ; 92 ].…”

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis

“…The negative super-ratio observed with miR-181 (interaction = −1.60) is also consistent with the miR-17 finding. In fact, miR-181 is induced by LIF, a cytokine which inhibits the proliferation of stem cells, and hence, it inhibits neurogenesis (Pati et al, 2014 ). One of the target of miR-181 is MCL1, which however, has two isoforms: while the isoform 1 is anti-apoptotic, the isoform 2 is pro-apoptotic.…”

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

“…50 Deregulated expression of hsa.miR.143 is present in synaptoneurosomes isolated from prion-infected mice at both asymptomatic and symptomatic stages of the disease. 57 The expression of hsa.miR.143 in neuronal stem cells is increased following the administration of insulinlike growth factor-1 58 (known to support the proliferation and enhanced survival of neuronal stem cells). 59 An analysis of the downstream cascade of hsa.miR.143 has exposed many potential targets, such as platelet-derived growth factor receptor-α, which play a significant role in the differentiation of oligodendrocytes, as trocytes, and neuroprogenitors.…”