miR-92a-2-5p Regulates the Proliferation and Differentiation of ASD-Derived Neural Progenitor Cells

Abstract

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with abnormal behavior. However, the pathogenesis of ASD remains to be clarified. It has been demonstrated that miRNAs are essential regulators of ASD. However, it is still unclear how miR-92a-2-5p acts on the developing brain and the cell types directly. In this study, we used neural progenitor cells (NPCs) derived from ASD-hiPSCs as well as from neurotypical controls to examine the effects of miR-92a-2-5p on ASD-NPCs proliferation and neuronal differentiation, and whether miR-92a-2-5p could interact with genetic risk factor, DLG3 for ASD. We observed that miR-92a-2-5p upregulated in ASD-NPCs results in decreased proliferation and neuronal differentiation. Inhibition of miR-92a-2-5p could promote proliferation and neuronal differentiation of ASD-NPCs. DLG3 was negatively regulated by miR-92a-2-5p in NPCs. Our results suggest that miR-92a-2-5p is a strong risk factor for ASD and potentially contributes to neuropsychiatric disorders.

Transition from Animal-Based to Human Induced Pluripotent Stem Cells (iPSCs)-Based Models of Neurodevelopmental Disorders: Opportunities and Challenges

“…Human sion, early differentiation deficits and reduced number of inhibitory neurons [307]. In addition, inhibition of this miRNA rescued the proliferation and differentiation deficits found in ASD NPCs, suggesting that miR-92a-2-5p may be a regulator of these processes, especially in inhibitory neurons.…”

“…It was previously shown that miR-92a plays an important role in neuronal neurite outgrowth, neuronal differentiation and GABAergic neuronal maturation [306]. Considering this, studies focusing on miR-92a-2-5p, which shares the same seed sequence as miR-92a, using NPCs derived from ASD-hIPSCs, revealed increased levels of miR-92a-2-5p concomitant with decreased proliferation, with a delay in S phase progression, early differentiation deficits and reduced number of inhibitory neurons [307]. In addition, inhibition of this miRNA rescued the proliferation and differentiation deficits found in ASD NPCs, suggesting that miR-92a-2-5p may be a regulator of these processes, especially in inhibitory neurons.…”

Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia

“…Specifically, we examined miR-451a and miR-486-3p that are most frequently altered in individuals with ASD [ 42 ], and miR-132-3p and miR-137-3p, known to be commonly altered in individuals with SCZ [ 12 , 43 ]. Additionally, we explored miR-21-5p, miR-92a-2-5p, miR-144-3p, and miR-146a-5p, all of which exhibit dysregulation in both ASD and SCZ individuals [ 12 , 42 , 44 , 45 , 46 , 47 ]. Furthermore, we placed a particular emphasis on examining these variations within the context of sexual dimorphism.…”