Breaking the barrier: CSF-producing choroid plexus organoids model pathogen and drug entry to the brain

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• Laura Pellegrini (LMB, Cambridge)
• Monday 07 February 2022, 14:30-15:30
• Online.

If you have a question about this talk, please contact Elena Scarpa.

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The choroid plexus (ChP) is a highly conserved and surprisingly understudied secretory tissue in the brain. This tissue displays a number of important functions in the brain such as forming a protective epithelial barrier and secreting the cerebrospinal fluid (CSF). The CSF is important for the maintenance of physiological levels of nutrients in the brain, for the transport of signalling molecules and growth factors and for its protective role in the regulation of intracranial pressure. To explore the role of the ChP-CSF system, we recently established a protocol to generate ChP organoids using a combination of signalling molecules that are physiologically present during the stages of development of this tissue. More interestingly, not only do these organoids develop the ChP but they also recapitulate fundamental functions of this tissue, namely secretion and formation of a tight epithelial barrier. Combining single-cell RNA -sequencing with immunohistochemical and EM validation, we detected the presence of ChP specific channels and transporters localised on the apical brush border of the ChP epithelium. By testing different compounds, we were able to demonstrate the selective permeability of the ChP barrier in vitro, using NMR . In addition, we noticed the formation of large fluid-filled cysts protruding from the organoids, the contents of which, analysed by mass spectrometry, highly resembles human CSF . Finally, we used this model to test pathogen entry in the brain and we infected the organoids with live SARS -CoV-2. We found that SARS -CoV-2 infects ChP epithelial cells causing damage of this key brain barrier. In conclusion, we believe this system represents an excellent tool to study pathogen and drug entry in the brain.

This talk is part of the Morphogenesis Seminar Series series.

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• Graduate-Seminars
• Morphogenesis Seminar Series
• Online

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