Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Actuation Enhances Patterning in Human Neural Tube Organoids

ABSTRACT: Tissues achieve their complex spatial organization though physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here we develop devices which enable the actuation of organoids, and show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). We demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for use of these tools in regenerative medicine and disease modelling applications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154120 | GEO | 2021/02/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

Project description:Organoids have huge therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, the clinical application is greatly limited by the lack of effective GMP-complaint systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide the instructive native environment necessary to direct cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation due to their natural, non-carcinogenic origin. We show that gels developed from decellularized porcine small intestinal mucosa have similar physiological range and mechanical properties to commercially available gels. ECM-derived gels enable formation and growth of endoderm-derived organoids and, moreover, supports in vivo organoid growth. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.

2019-11-05 | GSE135108 | GEO

KCNJ2 inhibition mitigates mechanical injury in human brain organoids [scRNA-seq]

Project description:Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the brain itself and which strategies most potently mitigate these processes, particularly in individuals genetically predisposed to neurodegeneration. We developed a high-intensity ultrasound platform to inflict mechanical injury to iPSC-derived cortical organoids. Mechanically injured organoids elicit several classic hallmarks of TBI including neuron death, tau phosphorylation, and TDP-43 phosphorylation and nuclear egress. We found that deep layer excitatory neurons were particularly vulnerable to injury and that TDP-43 proteinopathy promotes loss-of-function and cell death. Injured organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference screening, we identified a mechanosensory channel, KCNJ2, whose inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72 ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuron death after brain injury, and we present a scalable, genetically-flexible cerebral organoid model that may enable identification of additional modifiers downstream of mechanical stress.

2024-03-04 | GSE260532 | GEO

KCNJ2 inhibition mitigates mechanical injury in human brain organoids

2024-03-04 | GSE259432 | GEO

Single cell analysis of iPSC-derived cortical organoids in biofunctionalized gelatin hydrogels

Project description:Human neural organoid models have become an important tool for studying neurobiology. In this work, we compared Matrigel to an N-cadherin peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. Specifically, we compare five materials: (1) Matrigel, (2) GelMA-Cad with high crosslinker (HC), (3) GelMA-Cad with low crosslinker (LC), (4) GelMA HC and (5) GelMA LC. We determined that both mechanical properties and peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad produce higher numbers of neurogenic and ciliated radial glia and upper-layer excitatory neurons—an important population for modeling neurodegenerative disease—compared to GelMA and Matrigel controls.

2024-02-28 | E-MTAB-13828 | biostudies-arrayexpress

Decoupling the Biochemical and Mechanical Effects of Muscle Exercise on Motor Neurons with 2.5D Actuating Matrices

Project description:Muscles’ function as an endocrine organ is still poorly understood, but an emerging body of literature has provided evidence that myokines may aid in the development of surrounding tissues. Another outcome of muscle contraction in vivo is the localized mechanical forces produced. Current experimental techniques are not equipped to isolate and study the two effects independently. We have developed a system to culture contractile 2D optogenetic muscle long-term to provide a source for myokine secretion. We supplement our neuron monoculture with myokine secreted media and saw a 3X increase in total neurite length magnitude and a 3.2X increase in the rate of growth. As for mechanical stimulation, we optimize our Magnetic Matrix Actuation (MagMA) to provide localized stressors on the growing neurites. The mechanical stimulation regime results in a ~2.7X increase in both magnitude and rate of total neurite length. We validate our morphological findings with bulk RNA-sequencing analysis, the results show a large number of differentially expressed genes between the biochemical stimulation group and control. On the other hand, there was minimal difference between the mechanical stimulation group and control. Our study mechanistically unravels how repeated muscle contraction, or exercise, regulates motor neuron growth and maturation.

2024-02-25 | GSE257540 | GEO

Transcriptional profiling of mouse molar and incisor tooth organoids

Project description:Organoid models provide powerful tools to study tissue biology and development in a dish. Here, we established first-time organoid models from early-postnatal (postnatal day 7) mouse molar and incisor, capable of differentiation toward ameloblast-like cells in vitro. To more in detail characterise organoids from mouse molar and incisor, bulk RNA-sequencing was performed on the following (1) early passage (passage 0) organoids from both tooth types grown in basal tooth organoid medium (TOM) with or without addition of exogenous epidermal growth factor (EGF); and (2) late passage (passage 5) organoids grown in TOM+EGF or differentiation medium (DM).

2023-04-19 | E-MTAB-12557 | biostudies-arrayexpress

Single cell RNA-seq of hiPSC-derived kidney organoids differentiated within self-assembling peptide hydrogels and the animal-derived matrix Matrigel

Project description:scRNA-seq was used to characterise hiPSC-derived kidney organoids differentiated within fully synthetic self-assembling peptide hydrogels of variable mechanical strengths and compare these to organoids differentiated within the animal-derived matrix, Matrigel. Organoids were matured in the respective matrices until day 24 of differentiation and 6 organoids per support matrix were then pooled and dissociated using the cold-active protease from Bacillus licheniformis. Cells were processed on the 10x Genomics Chromium platform using the Single-Cell 3’ v3.1 protocol. The NextSeq500 (Illumina) was used to sequence the libraries generated and initial processing of the data was carried out using the 10X Genomic Cell Ranger v3.1.0 pipeline.

2022-10-31 | E-MTAB-11149 | biostudies-arrayexpress

Actuation Enhances Patterning in Human Neural Tube Organoids

Project description:Actuation Enhances Patterning in Human Neural Tube Organoids

| PRJNA645161 | ENA

Volumetric compression by heterogeneous scaffold embedding promotes cerebral organoid growth and maturation

Project description:While biochemical regulation has been extensively studied in cerebral organoid modeling protocols, the role of mechano-regulation in directing stem cell fate and organoid development has been relatively unexplored. Volumetric compression, a key aspect of natural brain development, is known to influence neuronal differentiation. However, stiff interpenetrating network compression fails to accurately replicate the dynamic organoid development observed in nature. In this study, we present a novel method of heterogeneous embedding using an alginate-shell-Matrigel-core system. This approach allows for cell-Matrigel remodeling by the inner layer and provides moderate normal compression through the soft alginate outer layer. Our results show significant improvements in cell proliferation and maturation of cerebral organoids, as evidenced by increased expression of neuronal markers such as neurofilament (NF) and microtubule-associated protein 2 (MAP2). Compared to non-alginate embedding and alginate compression groups, volume growth remains unimpeded. Our findings demonstrate the successful mechanical regulation of cerebral organoids, which not only mimics the mechanical environment of brain development but also exhibits a regular growth profile with enhanced maturation. These results highlight the importance and potential practical applications of mechano-regulation in the establishment of brain organoids.

2023-09-09 | GSE242715 | GEO

Prospective derivation of a 'Living Organoid Biobank' of colorectal cancer patients

Project description:In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design. We generated organoids from healthy tissue and coloncarcinoma tissue. The organoids were trypsinized, plated in matrigel and overlaid with medium. After three days, RNA was isolated using Qiagen RNAeasy. Medium conditions are the same for all organoids, irrespective of their origin.

2015-05-07 | E-GEOD-64392 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data