Multi-Region Brain Organoid: Fusion Organoid with Cerebral, Endothelial and Mid-Hindbrain Components DOI Creative Commons

Anannya Kshirsagar,

Hayk Mnatsakanyan,

Sai Kulkarni

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Brain organoid technology has revolutionized our ability to model human neurodevelopment in vitro. However, current techniques remain limited by their reliance on simplified endothelial cell populations rather than a complete system. We engineered Multi-Region Organoids (MRBOs) that integrate cerebral, mid/hindbrain, and complex organoids into one structure. Different from the earlier approaches based isolated HUVECs, contain diverse vascular types, including progenitors, mature cells, pericytes, proliferating angiogenic cells stromal cells. Our strategy employs sequential modulation of key developmental pathways generate individual organoids, followed optimized fusion conditions maintain regional identities while supporting cellular integration. Single-nucleus RNA sequencing shows MRBOs develop discrete neural specific each brain region alongside specialized establish paracrine signalling networks. Integration analysis with fetal data contribute 80% clusters found tissue (Carnegie stages 12-16), whereas CellChat identifies 13 previously uncharacterized endothelial-neural interactions. Notably, we uncover endothelial-derived factors support persistence intermediate progenitor during hindbrain development, but not cerebral thereby revealing new role for patterning. This platform enables matching multiple regions, fully incorporating nature at same time providing opportunities studying neurodevelopmental disorders which neural-endothelial interactions are disrupted. MRBO system establishes foundation investigating processes, an enabling context closer physiological relevance.

Язык: Английский

Multi-Region Brain Organoid: Fusion Organoid with Cerebral, Endothelial and Mid-Hindbrain Components DOI Creative Commons

Anannya Kshirsagar,

Hayk Mnatsakanyan,

Sai Kulkarni

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Brain organoid technology has revolutionized our ability to model human neurodevelopment in vitro. However, current techniques remain limited by their reliance on simplified endothelial cell populations rather than a complete system. We engineered Multi-Region Organoids (MRBOs) that integrate cerebral, mid/hindbrain, and complex organoids into one structure. Different from the earlier approaches based isolated HUVECs, contain diverse vascular types, including progenitors, mature cells, pericytes, proliferating angiogenic cells stromal cells. Our strategy employs sequential modulation of key developmental pathways generate individual organoids, followed optimized fusion conditions maintain regional identities while supporting cellular integration. Single-nucleus RNA sequencing shows MRBOs develop discrete neural specific each brain region alongside specialized establish paracrine signalling networks. Integration analysis with fetal data contribute 80% clusters found tissue (Carnegie stages 12-16), whereas CellChat identifies 13 previously uncharacterized endothelial-neural interactions. Notably, we uncover endothelial-derived factors support persistence intermediate progenitor during hindbrain development, but not cerebral thereby revealing new role for patterning. This platform enables matching multiple regions, fully incorporating nature at same time providing opportunities studying neurodevelopmental disorders which neural-endothelial interactions are disrupted. MRBO system establishes foundation investigating processes, an enabling context closer physiological relevance.

Язык: Английский

Процитировано

0