Extracellular vesicle-mediated trafficking of molecular cues during human brain development
Andrea Forero,
Fabrizia Pipicelli,
Sylvain Moser,
Natalia Baumann,
Christian Grätz,
Mariano Gonzalez Pisfil,
Michael W. Pfaffl,
Benno Pütz,
Pavel Kielkowski,
Filippo M. Cernilogar,
Giuseppina Maccarrone,
Rossella Di Giaimo,
Silvia Cappello
Affiliations
Andrea Forero
Max Planck Institute of Psychiatry, Munich, Germany; Division of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University (LMU), Munich, Germany
Fabrizia Pipicelli
Max Planck Institute of Psychiatry, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany
Sylvain Moser
Max Planck Institute of Psychiatry, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany
Natalia Baumann
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
Christian Grätz
Division of Animal Physiology and Immunology, Technical University of Munich, Freising, Germany
Mariano Gonzalez Pisfil
Core Facility Bioimaging and Walter-Brendel-Centre of Experimental Medicine, Biomedical Center, Ludwig Maximilian University, Munich, Germany
Michael W. Pfaffl
Division of Animal Physiology and Immunology, Technical University of Munich, Freising, Germany
Benno Pütz
Max Planck Institute of Psychiatry, Munich, Germany
Pavel Kielkowski
Department of Chemistry, Ludwig Maximilian University, Munich, Germany
Filippo M. Cernilogar
Division of Molecular Biology, Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University, Munich, Germany; Department of Science and Technological Innovation, University of Piemonte Orientale, Alessandria, Italy
Giuseppina Maccarrone
Max Planck Institute of Psychiatry, Munich, Germany
Rossella Di Giaimo
Max Planck Institute of Psychiatry, Munich, Germany; Department of Biology, University of Naples Federico II, Naples, Italy; Corresponding author
Silvia Cappello
Max Planck Institute of Psychiatry, Munich, Germany; Division of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University (LMU), Munich, Germany; Corresponding author
Summary: Cellular crosstalk is an essential process influenced by numerous factors, including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neurodegenerative disorders, but whether EVs display cell-type-specific features for cellular crosstalk during neurodevelopment is unknown. Here, using human-induced pluripotent stem cell-derived cerebral organoids, neural progenitors, neurons, and astrocytes, we identify heterogeneity in EV protein content and dynamics in a cell-type-specific and time-dependent manner. Our results support the trafficking of key molecules via EVs in neurodevelopment, such as the transcription factor YAP1, and their localization to differing cell compartments depending on the EV recipient cell type. This study sheds new light on the biology of EVs during human brain development.
