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Sergiu Pașca is a faculty member at Stanford University, where he is also the Uytengsu Director of the Stanford Brain Organogenesis Program. He is a pioneer in developing 3D brain-region-specific organoids, assembloids and cellular models of neuropsychiatric disease from stem cells.

Neural differentiation and self-organization of hPSCs are induced by culture in suspension. Neural spheroids are then differentiated into dorsal or ventral forebrain spheroids that can be combined to obtain functionally integrated human assembloids.

Addition of an inexpensive, biocompatible polymer reduces spontaneous fusions of organoids in culture.

Cortical organoids derived from tetraploid human–chimpanzee fused induced pluripotent stem cells provide a platform for untangling unique molecular features of human brain development.

Andersen, Thom and colleagues reveal the single-cell-resolution transcriptome of the midgestation human spinal cord and discover remarkable heterogeneity across and within cell types.

This protocol combines pooled CRISPR–Cas9 screening with neural organoid and assembloid models and illustrates how it can be applied to map hundreds of disease genes onto cellular pathways and specific aspects of human neural development.

A new technique, in which forebrain-precursor cells are ablated from early-stage mouse embryos and replaced with embryonic stem cells, promises to facilitate our ability to study the central nervous system.

Two groups have grown self-organizing models of mouse embryos from stem cells in vitro. The models mimic mid-gestation embryos, providing an unparalleled opportunity to study early embryonic development.

Assembloids are integrated with CRISPR screening to investigate the involvement of 425 neurodevelopmental disorder genes in human interneuron development, showing endoplasmic reticulum displacement before nuclear translocation and interference from LNPK deletion, resulting in abnormal migration.

Electrical activity in neural organoids is captured with a device inspired by a paper-cutting art.

A human ascending somatosensory assembloid model was developed, which integrates multiple organoids to simulate the spinothalamic pathway, demonstrating functional connectivity and responsiveness to stimuli and revealing insights into pain-related genetic mutations.

Difficult questions will be raised as models of the human brain get closer to replicating its functions, explain Nita A. Farahany, Henry T. Greely and 15 colleagues.

Brain organoids derived from human iPSCs are used to study the effects of hypoxia on early cortical neurodevelopment and identify defects in specific human progenitor populations that likely contribute to encephalopathy of prematurity.

A protocol adapted to xeno- and feeder-free conditions is shown to generate reliable and consistent cortical brain organoids across differentiations and source stem cell lines, making it suitable for disease modeling and other applications.

Antisense oligonucleotides effectively decrease the inclusion of exon  8A of CACNA1C in human cells both in vitro and in rodents transplanted with human brain organoids, and a single intrathecal administration rescued both calcium changes and in vivo dendrite morphology of patient neurons.

A human neural organoid cell atlas integrating 36 single-cell transcriptomic datasets shows cell types and states and estimates transcriptomic similarity between primary and organoid counterparts, showing potential to assess organoid fidelity and facilitate protocol development.

Bioprinting has potential in the biofabrication of three dimensional tissues, but is poorly suited to the manipulation of neural organoids. Here, the authors develop a bioprinting platform to allow the arrangement of organoids to form assembloids.

Human stem cell-derived cortical organoids transplanted into rats mature and integrate into sensory and motivation circuits to influence behaviour.

The nomenclature for human multicellular models of nervous system development and disease, including organoids, assembloids and transplants, is discussed and a consensus framework is presented.

NeuroString, a tissue-like biological interface created by laser patterning of polyimide into a graphene/nanoparticle network embedded in an elastomer, is introduced, allowing in vivo real-time detection of neurotransmitters in the brain and gut.

Nano-bio interfaces enable communication between synthetic materials and biological systems at the nanoscale, with their functionality shaped by material properties, surface chemistry and topography. This Review discusses the key considerations and methods for engineering nano-bio interfaces for bioelectrical signal detection and biochemical signal transduction.

Organoids representing the human striatum are generated and used to build circuits in cortico-striatal assembloids.

Gordon et al. use genome-wide unbiased approaches to show that human cerebral cortical organoids, when cultured for many months, start to resemble stages of postnatal brain development, with a timeline that parallels in vivo development.

Single-cell and bulk transcriptomics of adult human microglia from a population of individuals reveals activated states across several brain disorders and maps Alzheimer’s disease variants to microglia-enriched genes.

Human brain organoids are endowed with regional topography using engineered signaling centers.

The transplantation of human cortical organoids in rats enables maturation and integration of human neural cells that can engage with the host circuitry, providing a framework to study alterations in morphology and physiology of patient-derived tissue.

The authors generate 3D brain organoids containing oligodendrocytes, astrocytes, and neurons derived from human pluripotent stem cells. These human oligodendrocytes are transcriptionally similar to primary cells and mature to myelinate axons.

A protocol is described for generating human brain assembloids and performing viral labeling and retrograde tracing, 3D live imaging of axon projection and optogenetics with calcium imaging and electrophysiological recordings to model neural circuits.

An international group of neuroscience researchers presents a framework for experimental designs for research using neural organoids and assembloids to study human development, evolution and disease.