What has single-cell transcriptomics taught us about long non-coding RNAs in the ventricular-subventricular zone?

Abstract

Long non-coding RNA (lncRNA) function is mediated by the process of transcription or through transcript-dependent associations with proteins or nucleic acids to control gene regulatory networks. Many lncRNAs are transcribed in the ventricular-subventricular zone (V-SVZ), a postnatal neural stem cell niche. lncRNAs in the V-SVZ are implicated in neurodevelopmental disorders, cancer, and brain disease, but their functions are poorly understood. V-SVZ neurogenesis capacity declines with age due to stem cell depletion and resistance to neural stem cell activation. Here we analyzed V-SVZ transcriptomics by pooling current single-cell RNA-seq data. They showed consistent lncRNA expression during stem cell activation, lineage progression, and aging. In conjunction with epigenetic and genetic data, we predicted V-SVZ lncRNAs that regulate stem cell activation and differentiation. Some of the lncRNAs validate known epigenetic mechanisms, but most remain uninvestigated. Our analysis points to several lncRNAs that likely participate in key aspects of V-SVZ stem cell activation and neurogenesis in health and disease.