Maturation and circuit integration of transplanted human cortical organoids

Nature, Journal Year: 2022, Volume and Issue: 610(7931), P. 319 - 326

Published: Oct. 12, 2022

Abstract Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease 1–5 . However, lack the connectivity that exists vivo, limits maturation makes integration other circuits control behaviour impossible. Here we show stem cell-derived cortical transplanted into somatosensory cortex of newborn athymic rats develop mature cell types integrate sensory motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple lines animals, whereas single-nucleus profiling shows progression corticogenesis emergence activity-dependent transcriptional programs. Indeed, neurons display more complex morphological, synaptic intrinsic membrane properties than their counterparts, enables discovery defects derived from individuals Timothy syndrome. Anatomical functional tracings receive thalamocortical corticocortical inputs, vivo recordings activity demonstrate these inputs can produce responses cells. Finally, extend axons throughout rat brain optogenetic activation drive reward-seeking behaviour. Thus, engage host We anticipate this approach will be useful for detecting circuit-level phenotypes patient-derived cells cannot otherwise uncovered.

Language: Английский

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A nomenclature consensus for nervous system organoids and assembloids

Nature, Journal Year: 2022, Volume and Issue: 609(7929), P. 907 - 910

Published: Sept. 28, 2022

Language: Английский

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Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3770 - 3788.e27

Published: Sept. 1, 2022

Language: Английский

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Genetics of human brain development

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

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Spatially controlled construction of assembloids using bioprinting

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 19, 2023

Abstract The biofabrication of three-dimensional (3D) tissues that recapitulate organ-specific architecture and function would benefit from temporal spatial control cell-cell interactions. Bioprinting, while potentially capable achieving such control, is poorly suited to organoids with conserved cytoarchitectures are susceptible plastic deformation. Here, we develop a platform, termed Spatially Patterned Organoid Transfer (SPOT), consisting an iron-oxide nanoparticle laden hydrogel magnetized 3D printer enable the controlled lifting, transport, deposition organoids. We identify cellulose nanofibers as both ideal biomaterial for encasing magnetic nanoparticles shear-thinning, self-healing support maintaining positioning facilitate generation assembloids. leverage SPOT create precisely arranged assembloids composed human pluripotent stem cell-derived neural patient-derived glioma In doing so, demonstrate potential platform construct which key developmental processes disease etiologies.

Language: Английский

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Multi-omic profiling of the developing human cerebral cortex at the single-cell level

Science Advances, Journal Year: 2023, Volume and Issue: 9(41)

Published: Oct. 12, 2023

The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that mediated, part, by spatiotemporal activity cis-regulatory elements (CREs). We simultaneously profiled and chromatin accessibility 45,549 cortical nuclei across six broad developmental time points from fetus to adult. identified cell type-specific domains which highly correlated with expression. Differentiation pseudotime trajectory analysis indicates at CREs precedes transcription structure play a critical role neuronal lineage commitment. In addition, we mapped temporally specific genetic loci implicated neuropsychiatric traits, including schizophrenia bipolar disorder. Together, our results describe complex regulation composition stages determination shed light on impact alterations disease.

Language: Английский

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Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 22, 2024

Language: Английский

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Spatiotemporal, optogenetic control of gene expression in organoids

Nature Methods, Journal Year: 2023, Volume and Issue: 20(10), P. 1544 - 1552

Published: Sept. 21, 2023

Organoids derived from stem cells have become an increasingly important tool for studying human development and modeling disease. However, methods are still needed to control study spatiotemporal patterns of gene expression in organoids. Here we combined optogenetics perturbation technologies activate or knock-down RNA target genes programmable patterns. To illustrate the usefulness our approach, locally activated Sonic Hedgehog (SHH) signaling organoid model neurodevelopment. Spatial single-cell transcriptomic analyses showed that this local induction was sufficient generate stereotypically patterned organoids revealed new insights into SHH's contribution regulation With study, propose optogenetic perturbations combination with spatial transcriptomics as a powerful technology reprogram cell fates tissue patterning

Language: Английский

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Human fetal brain self-organizes into long-term expanding organoids

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 712 - 732.e38

Published: Jan. 8, 2024

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, solely established pluripotent stem cells. Here, we show that healthy human fetal in vitro self-organizes into (FeBOs), phenocopying aspects of vivo cellular heterogeneity and complex organization. FeBOs expanded over long time periods. FeBO growth requires maintenance integrity, which ensures production tissue-like extracellular matrix (ECM) niche, ultimately endowing expansion. lines derived different areas the central nervous system (CNS), including dorsal ventral forebrain, preserve their regional identity allow probe positional identity. Using CRISPR-Cas9, showcase generation syngeneic mutant for study cancer. Taken together, constitute complementary CNS organoid platform.

Language: Английский

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Modeling embryo-endometrial interface recapitulating human embryo implantation

Science Advances, Journal Year: 2024, Volume and Issue: 10(8)

Published: Feb. 23, 2024

The initiation of human pregnancy is marked by the implantation an embryo into uterine environment; however, underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)–EMO, which emulate in vivo architecture tissue. AO-EMO comprise exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network. When cocultured with embryonic stem cell–derived blastoids, three-dimensional feto-maternal assembloid system recapitulates critical stages, including apposition, adhesion, invasion. Endometrial epithelial cells were subsequently disrupted syncytial invade fuse cells. We validated fusion syncytiotrophoblasts using blastocysts. Our model provides foundation for investigating interactions, offering valuable insights advancing reproductive medicine.

Language: Английский

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