| Autor: |
Narasipura SD, Zayas JP, Ash MK, Reyes A, Shull T, Gambut S, Schneider JR, Lorenzo-Redondo R, Al-Harthi L, Mamede JI |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 20. Date of Electronic Publication: 2024 Jun 20. |
| DOI: |
10.1101/2024.06.13.598579 |
| Abstrakt: |
Cerebral organoids (COs) are a valuable tool to study the intricate interplay between glial cells and neurons in brain development and disease, including HIV-associated neuroinflammation. We developed a novel approach to generate microglia containing COs (CO-iMs) by co-culturing hematopoietic progenitors and induced pluripotent stem cells. This approach allowed for the differentiation of microglia within the organoids concomitantly to the neuronal progenitors. CO- iMs exhibited higher efficiency in generation of CD45 + /CD11b + /Iba-1 + microglia cells compared to conventional COs with physiologically relevant proportion of microglia (∼7%). CO-iMs exhibited substantially higher expression of microglial homeostatic and sensome markers as well as markers for the complement cascade. CO-iMs showed susceptibility to HIV infection resulting in a significant increase in several pro-inflammatory cytokines/chemokines and compromised neuronal function, which were abrogated by addition of antiretrovirals. Thus, CO-iM is a robust model to decipher neuropathogenesis, neurological disorders, and viral infections of brain cells in a 3D culture system. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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