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Title: | Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia |
Author: | Canals, Isaac Comella Bolla, Andrea Cepeda-Prado, Efrain Avaliani, Natalia Crowe, James A. Oburoglu, Leal Bruzelius, Andreas King, Naomi Pajares, María A. Pérez-Sala, Dolores Heuer, Andreas Rylander Ottosson, Daniella Soriano i Fradera, Jordi Ahlenius, Henrik |
Keywords: | Electrofisiologia Cèl·lules mare Astròcits Electrophysiology Stem cells Astrocytes |
Issue Date: | 18-May-2023 |
Publisher: | Oxford University Press |
Abstract: | Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/braincomms/fcad158 |
It is part of: | Brain Communications, 2023, vol. 5, num. 3, p. 1-16 |
URI: | http://hdl.handle.net/2445/200656 |
Related resource: | https://doi.org/10.1093/braincomms/fcad158 |
ISSN: | 2632-1297 |
Appears in Collections: | Articles publicats en revistes (Física de la Matèria Condensada) Articles publicats en revistes (Institut de Recerca en Sistemes Complexos (UBICS)) |
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