Human neural rosettes secrete extracellular vesicles enriched in neural and glial cellular components including the proteolipid protein 1

BERTONE AROLFO, MATÍAS; CESCHIN, DANILO; REMEDI, MÓNICA; CÁCERES, ALFREDO; HERRERA LÓPEZ, MALENA; GASTALDI, LAURA; MOYANO, ANA LIS

Congreso; XVIII Meeting of the Chilean Society for Neuroscience; 2022

Sociedad Chilena de Neurociencias

Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed nanovesicles that shuttle bioactive molecules (e.g. proteins, lipids and RNAs) between cells. EVs participate in stem cell renewal and differentiation during central nervous system (CNS) development. Human neural rosettes (hNRs) are radial structures of neuroepithelial cells that assemble from human induced pluripotent stem cells (hiPSCs) differentiation into neural and glial cells. hNRs are an in vitro model that recapitulates some stages of the neural tube morphogenesis and expresses molecular components expressed in vivo during CNS development. Here we showed that hiPSCs and hNRs secrete EVs (hiPSC-EVs and hNR-EVs, respectively) enriched in proteins associated with EVs and the endomembrane system. hNR-EVs are specifically enriched in cellular components from neural and glial origin. Remarkably, among glial-derived components associated with hNR-EVs we found the myelin proteolipid protein (PLP1). Although PLP1 is the major protein of myelin in the CNS it is also expressed at embryonic stages in animals, i.e., long before myelin is assembled. Through in silico analysis we showed that hNRs express PLP1 at various time points during development and different culture conditions. Moreover, PLP1 localizes radially along the lumen and edges of hNRs. These results indicate that EVs secreted by hNRs exhibit neural and glial cellular components and might provide an innovative approach to study human neural tube formation and EVs biological activity during CNS development.