Deriving early single-rosette brain organoids from human pluripotent stem cells

Stem Cell Reports, Год журнала: 2023, Номер 18(12), С. 2498 - 2514

Опубликована: Ноя. 22, 2023

Brain organoid methods are complicated by multiple rosette structures and morphological variability. We have developed a human brain technique that generates self-organizing, single-rosette cortical organoids (SOSR-COs) with reproducible size structure at early timepoints. Rather than patterning 3-dimensional embryoid body, we initiate formation from 2-dimensional monolayer of pluripotent stem cells patterned small molecules into neuroepithelium differentiated to the developing dorsal cerebral cortex. This approach recapitulates 2D 3D developmental transition neural plate tube. Most fragments form spheres single central lumen. Over time, SOSR-COs develop appropriate progenitor laminar cell types as shown immunocytochemistry single-cell RNA sequencing. At time points, this method demonstrates robust structural phenotypes after chemical teratogen exposure or when modeling genetic neurodevelopmental disorder, should prove useful for studies development disease modeling.

Язык: Английский

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Bioengineering tools for next-generation neural organoids

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 103011 - 103011

Опубликована: Март 24, 2025

Язык: Английский

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Human assembloid model of the ascending neural sensory pathway

Nature, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Somatosensory pathways convey crucial information about pain, touch, itch and body part movement from peripheral organs to the central nervous system1,2. Despite substantial needs understand how these assemble develop pain therapeutics, clinical translation remains challenging. This is probably related species-specific features lack of in vitro models polysynaptic pathway. Here we established a human ascending somatosensory assembloid (hASA), four-part generated pluripotent stem cells that integrates somatosensory, spinal, thalamic cortical organoids model spinothalamic Transcriptomic profiling confirmed presence key cell types this circuit. Rabies tracing calcium imaging showed sensory neurons connect dorsal spinal cord neurons, which further neurons. Following noxious chemical stimulation, hASA demonstrated coordinated response. In addition, extracellular recordings revealed synchronized activity across assembloid. Notably, loss sodium channel NaV1.7, causes insensitivity, disrupted synchrony hASA. By contrast, gain-of-function SCN9A variant associated with extreme disorder induced hypersynchrony. These experiments ability functionally essential components pathway, could accelerate our understanding circuits facilitate therapeutic development.

Язык: Английский

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Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Emerging approaches to enhance human brain organoid physiology

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.

Язык: Английский

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Modeling forebrain regional development and connectivity by human brain organoids

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 91, С. 102324 - 102324

Опубликована: Фев. 20, 2025

Язык: Английский

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Exploring human brain development and disease using assembloids

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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CellFlow enables generative single-cell phenotype modeling with flow matching

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

Опубликована: Апрель 17, 2025

Abstract High-content phenotypic screens provide a powerful strategy for studying biological systems, but the scale of possible perturbations and cell states makes exhaustive experiments unfeasible. Computational models that are trained on existing data extrapolate to correctly predict outcomes in unseen contexts have potential accelerate discovery. Here, we present CellFlow, flexible framework based flow matching can model single phenotypes induced by complex perturbations. We apply CellFlow various screens, accurately predicting expression responses wide range perturbations, including cytokine stimulation, drug treatments gene knockouts. successfully modeled developmental at whole-embryo guided fate organoid engineering heterogeneous populations arising from combinatorial morphogen performing virtual protocol screen. Taken together, has discovery learning generating conditions.

Язык: Английский

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Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Bioengineering innovations for neural organoids with enhanced fidelity and function

Cell stem cell, Год журнала: 2025, Номер 32(5), С. 689 - 709

Опубликована: Май 1, 2025

Язык: Английский

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