Identification of miRNomes associated with adult neurogenesis after stroke using Argonaute 2-based RNA sequencing

ABSTRACT

Neurogenesis is associated with functional recovery after stroke. However, the underlying molecular mechanisms have not been fully investigated. Using an Ago2-based RNA immunoprecipitation to immunoprecipated Ago2-RNA complexes followed by RNA sequencing (Ago2 RIP-seq) approach, we profiled the miRNomes in neural progenitor cells (NPCs) harvested from the subventricular zone (SVZ) of the lateral ventricles of young adult rats. We identified more than 7 and 15 million reads in normal and ischemic NPC libraries, respectively. We found that stroke substantially changed Ago2-associated miRNA profiles in NPCs compared to those in non-ischemic NPCs. We also discovered a new complex repertoire of isomiRs and multiple miRNA-miRNA* pairs and numerous novel miRNAs in the non-ischemic and ischemic NPCs. Among them, pc-3p-17172 significantly regulated NPC proliferation and neuronal differentiation. Collectively, the present study reveals profiles of Ago2-associated miRNomes in non-ischemic and ischemic NPCs, which provide a molecular basis to further investigate the role of miRNAs in mediating adult neurogenesis under physiological and ischemic conditions.

KEYWORDS:

• Ago2
• microRNA
• neural progenitor cells
• neurogenesis
• RNA sequencing
• stroke

Disclosure of potential confllicts of interest

No potential conflicts of interest were disclosed.

Funding

This work was supported by AHA Grant-in-Aid 14GRNT20460167 (XSL), National Institutes of Health Grants RO1 RDK102861A (XSL), RO1 NS075156 (ZGZ) and RO1 NS088656 (MC).