Abstract
Human brain organoids cultured from human pluripotent stem cells provide a promising platform to recapitulate histological features of the human brain and model neural disorders. However, unlike animal models, brain organoids lack a reproducible topographic organization, which limits their application in modeling intricate biology, such as the interaction between different brain regions. To overcome these drawbacks, brain organoids have been pre-patterned into specific brain regions and fused to form an assembloid that represents reproducible models recapitulating more complex biological processes of human brain development and neurological diseases. This approach has been applied to model interneuron migration, neuronal projections, tumor invasion, oligodendrogenesis, forebrain axis establishment, and brain vascularization. In this review article, we will summarize the usage of this technology to understand the fundamental biology underpinning human brain development and disorders.
Highlights
The human central nervous system (CNS) develops from several distinct vesicles into multiple intertwined regions
We summarize the potential and great diversity of brain organoid fusion and co-culture models in studying human brain development and neural disorders
When fusing ventral forebrain organoids (VFOs) and dorsal forebrain organoids (DFOs) into fused forebrain organoids (FFOs), they found that dorsally born OLs outnumber ventral-derived OLs and become dominant in FFOs after long-term culture, During brain development, topographic structures are generated by gradients of various signaling activities, such as WNT, Sonic Hedgehog (SHH), and BMP (Petros et al, 2011), that regulate cell fate determination and regional identities
Summary
The human central nervous system (CNS) develops from several distinct vesicles into multiple intertwined regions. Fused Organoids for Brain Investigation organoids overcome many limitations imposed by animal models, providing a unique tool to study early stages of the human brain development under both physiological and pathological conditions (Lancaster and Knoblich, 2014b; Fatehullah et al, 2016). This organoid fusion technology has already been applied for the study of interneuron migration (Bagley et al, 2017; Birey et al, 2017; Xiang et al, 2017), brain circuits (Giandomenico et al, 2019; Xiang et al, 2019), oligodendrogenesis (Xiang et al, 2017; Kim et al, 2019), and to establish the dorsoventral and anteroposterior axes within forebrain organoids (Cederquist et al, 2019).
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