Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids

hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids

Generation of Functional Human 3D Cortico-Motor Assembloids

Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells

Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets

Midbrain_organoid_Treutlein

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

Autism genes converge on asynchronous development of shared neuron classes

Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells

Individual brain organoids reproducibly form cell diversity of the human cerebral cortex

Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells

Cell stress in cortical organoids impairs molecular subtype specification

Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures

Human CNS barrier-forming organoids with cerebrospinal fluid production

Assembly of functionally integrated human forebrain spheroids

Human cerebellar organoids with functional Purkinje cells

Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation

Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development

Reliability of human cortical organoid generation

Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids

Inferring and perturbing cell fate regulomes in human brain organoids

ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids

Androgens increase excitatory neurogenic potential in human brain organoids

CZ_CELLXGENE

HNOCA Extended: The Human Neural Organoid Atlas

The Human Neural Organoid Atlas

An integrated transcriptomic cell atlas of human neural organoids v1.0

Development of a quantitative prediction algorithm for target organ-specific similarity of human pluripotent stem cell-derived organoids and cells

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver

Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease

Progenitor identification and SARS-CoV-2 infection in human distal lung organoids

Single-cell atlas of human liver development reveals pathways directing hepatic cell fates

Suspension culture promotes serosal mesothelial development in human intestinal organoids

The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

An organoid‐derived bronchioalveolar model for SARS‐CoV‐2 infection of human alveolar type II‐like cells

Single cell RNA sequencing for the paired TNF-free and -treated intestinal organoids

Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

Human branching cholangiocyte organoids recapitulate functional bile duct formation

Human alveolar progenitors generate dual lineage bronchioalveolar organoids

Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip

Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles

Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection

Systematic evaluation of colorectal cancer organoid system by single-cell RNA-Seq analysis

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells

Single-Cell RNA-Seq Reveals that CD9 Is a Negative Marker of Glucose-Responsive Pancreatic β-like Cells Derived from Human Pluripotent Stem Cells

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Gene Regulatory Network Analysis and Engineering Directs Development and Vascularization of Multilineage Human Liver Organoids

Use of human tissue stem cell-derived organoid cultures to model enterohepatic circulation

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids

Generation of functional ciliated cholangiocytes from human pluripotent stem cells

A human liver organoid screening platform for DILI risk prediction

EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids

Development of human alveolar epithelial cell models to study distal lung biology and disease

An integrated transcriptomic cell atlas of human endoderm-derived organoids

Self-organized stem cell-derived human lung buds with proximo-distal patterning and novel targets of SARS-CoV-2

Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition

Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids

Differentiation of human pluripotent stem cells into functional airway basal stem cells

Multilineage communication regulates human liver bud development from pluripotency

Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands

Single‐cell analyses reveal SARS‐CoV‐2 interference with intrinsic immune response in the human gut

Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn’s Disease

Single cell analysis of Monolayer and Organoid Primary Prostate Human Epithelial Cells Derived from the same patient

A human multi-lineage hepatic organoid model for liver fibrosis

Maturation of human intestinal epithelium from pluripotency in vitro

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Integrated human endoderm-derived organoids cell atlas (HEOCA) v1.0

Organoid Network

An integrated transcriptomic cell atlas of human neural organoids v1.0 - Source Datasets

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.

Identification of neural oscillations and epileptiform changes in human brain organoids.

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR–Cas9 scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore clonality and lineage dynamics during cerebral organoid development and identify a time window of fate restriction as well as variation in neurogenic dynamics between progenitor neuron families.

Lineage recording in human cerebral organoids.

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease.

Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.

The purpose of this project is to assess the relevance of pluripotent stem cell-derived cerebral and liver organoids to recapitulate the variation in cell-type specific gene expression programs between individuals. Towards this aim, we will generate reference atlases of the developing cortex and liver from multiple individuals, derive iPSC lines from these same individuals, and determine if inter-individual gene expression variation is recapitulated in cerebral and liver organoids from the same individual from which we have reference maps. In parallel we will assess the genetic contribution to variablity between organoids from different iPSCs of multiple human individuals that are available in existing iPSC resources (e.g. HipSci).

Organoid single-cell genomic atlas uncovers human-specific features of brain development

Project Title	Species	Method	Anatomical Entity	Disease (Donor)	Cell Count Est.
Androgens increase excitatory neurogenic potential in human brain organoids	--	--	--	--	--
Assembly of functionally integrated human forebrain spheroids	--	--	--	--	--
Autism genes converge on asynchronous development of shared neuron classes	--	--	--	--	--
Cell stress in cortical organoids impairs molecular subtype specification	--	--	--	--	--
Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development	--	--	--	--	--
Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids	--	--	--	--	--
Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures	--	--	--	--	--
ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids	--	--	--	--	--
Generation of Functional Human 3D Cortico-Motor Assembloids	--	--	--	--	--
Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells	--	--	--	--	--
Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells	--	--	--	--	--
Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets	--	--	--	--	--
hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids	--	--	--	--	--
Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells	--	--	--	--	--
Human cerebellar organoids with functional Purkinje cells	--	--	--	--	--
Human CNS barrier-forming organoids with cerebrospinal fluid production	--	--	--	--	--
Identification of neural oscillations and epileptiform changes in human brain organoids.	Homo sapiens	10x 3' v3	zone of skin	Rett syndrome	54,942
Individual brain organoids reproducibly form cell diversity of the human cerebral cortex	--	--	--	--	--
Inferring and perturbing cell fate regulomes in human brain organoids	--	--	--	--	--
Lineage recording in human cerebral organoids.	Homo sapiens	3 library construction methods	skin of body	normal	103,520
Midbrain_organoid_Treutlein	--	--	--	--	--
Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.	Homo sapiens	10x 3' v2	skin of body	normal 3 diseases	Unspecified
Organoid single-cell genomic atlas uncovers human-specific features of brain development	Homo sapiens	5 library construction methods	3 anatomical entities	normal	19,916
Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex	--	--	--	--	--
Reliability of human cortical organoid generation	--	--	--	--	--
Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids	--	--	--	--	--
Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation	--	--	--	--	--