Intracellular and Extracellular Vesicle miRNA Signatures in Human iPSC-Derived Neural Stem Cells and Floor Plate Progenitors

Abstract

Refined control of intrinsic and extrinsic signals is critical for specific neuronal differentiation. Here, we differentiated human induced pluripotent stem cells (hiPSCs) from three different healthy donors into neural stem cells (NSCs) and floor plate progenitors (FPPs; progenitors of dopaminergic neurons) and further performed intracellular and extracellular vesicles' (EVs) miRNA profiling. While NSC and FPP cells differed significantly in levels of only 8 intracellular miRNAs, their differences were more evident in the EV miRNAs with 27 differentially expressed miRNAs. Target validation of intracellular miRNAs revealed that FPPs expressed more EXOC5 mRNA than NSCs, which is implicated in the function of primary cilia, an essential signaling organelle in FPPs. Moreover, we found a group of 5 miRNAs consistently enriched in EVs from these three cell types. This study presents a foundation for the field of miRNA regulation in neural development and provides new insights for disease modeling and regenerative medicine.

Keywords: EXOC5; dopaminergic neurons; exosomes; floor plate progenitors; human induced pluripotent stem cells; microRNA; neural differentiation; neuronal development.