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In Vivo Imaging Reveals Exosome-Mediated Intercellular Communication in Lens Development

ABSTRACT: The transparency of lens relies on proper intercellular communication. Exosomes are crucial mediators of intercellular communication and play a key role in organ homeostasis and development. However, their presence and dynamics in the lens remain unclear. This study aimed to investigate the existence of endogenous exosomes in the lens and explore their potential functions. Using the cryaa promoter to drive Cd63-AcGFP expression, we achieved lens-specific exosome labeling in zebrafish. Live imaging revealed the presence of exosomes in lens cells during development and their movement trajectory under physiological conditions. Additionally, lens-derived exosomes (lens-Exos) facilitate communication not only between lens cells but also with surrounding tissues. We also identified that the biogenesis of Cd63+ exosomes in the lens is regulated by the Syntenin-a pathway. As knockdown of Syntenin-a in zebrafish resulted in delayed lens development, indicating a potential role for exosomes in normal lens development. Furthermore, in vitro hESC-lentoid induction showed that extracellular vesicles from ROR1+ lens progenitor cells (ROR1+ LPCs-EVs) promote lentoid differentiation. Proteomic analysis provided insights into the functions of ROR1+ LPCs-EVs. Overall, our study is the first to observe endogenous exosomes in the lens, providing new insights into lens pathophysiology and a potential strategy for modulating the lens microenvironment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE298454 | GEO | 2025/10/30

REPOSITORIES: GEO

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Project description:The role of extracellular vesicles (EVs), specifically exosomes, in intercellular communication likely plays a key role in placental orchestration of pregnancy and maternal immune sensing of the fetus. While murine models are powerful tools to study pregnancy and maternal-fetal immune interactions, in contrast to human placental exosomes, the content of murine placental and pregnancy exosomes remains largely understudied. Using a recently developed in vitro culture technique, murine trophoblast stem cells derived from B6 mice were differentiated into syncytial-like cells. EVs from the conditioned media, as well as from pregnant and non-pregnant sera, were enriched for exosomes. The RNA composition of these murine trophoblast-derived and pregnancy-associated exosome-enriched-EVs (ExoE-EVs) was determined using RNA-sequencing analysis and expression levels confirmed by qRT-PCR. Differentially abundant miRNAs were detected in syncytial differentiated ExoE-EVs, particularly from the X chromosome cluster (mmu-miR-322-3p, mmu-miR-322-5p, mmu-miR-503-5p, mmu-miR-542-3p, and mmu-miR-450a-5p). These were confirmed to be increased in pregnant mouse sera ExoE-EVs by qRT-PCR analysis. Interestingly, fifteen miRNAs were only present within the pregnancy-derived ExoE-EVs compared to non-pregnant controls. Mmu-miR-292-3p and mmu-miR-183-5p were noted to be some of the most abundant miRNAs in syncytial ExoE-EVs and were also present at higher levels in pregnant versus non-pregnant sera ExoE-EVs. The bioinformatics tool, MultiMir, was employed to query publicly available databases of predicted miRNA-target interactions. This analysis reveals that the X-chromosome miRNAs are predicted to target ubiquitin-mediated proteolysis and intracellular signaling pathways. Knowing the cargo of placental and pregnancy-specific ExoE-EVs as well as the predicted biological targets informs studies using murine models to examine not only maternal-fetal immune interactions but also the physiologic consequences of placental-maternal communication.

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In Vivo Imaging Reveals Exosome-Mediated Intercellular Communication in Lens Development

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