Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components

Abstract

Extracellular vesicles (EVs) play a critical role in the development of neural cells in the central nervous system (CNS). Human neural rosettes (hNRs) are radial cell structures that assemble from induced pluripotent stem cells (hiPSCs) and recapitulate some stages of neural tube morphogenesis. Here we show that hiPSCs and hNRs secrete EVs (hiPSC-EVs and hNR-EVs) with distinct protein cargoes. Remarkably, hNR-EVs carry neuronal and glial cellular components involved in CNS development. By in silico analysis, we found hNR-EVs protein signature is expressed in vivo and in vitro during human brain development. Importantly, hNR-EVs stimulate hiPSCs to change their cellular morphology with a significant reduction in the pluripotency regulator SOX2. Interestingly, these effects were inhibited by antibodies against an unexpected neuroglial cargo of hNR-EVs: the major proteolipid protein (PLP1). These findings show that hNRs secrete bioactive EVs containing neural components and might contribute as trophic factors during human CNS development.