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RNA-seq of transplanted Human Intestinal Organoids differentiated with and without PVDF-TrFE Substrate

ABSTRACT: RNA-seq of transplanted Human Intestinal Organoids differentiated with and without PVDF-TrFE Substrate

PROVIDER: PRJEB70733 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR12329509_1.fastq.gz	Fastqsanger.gz
	ERR12329509_2.fastq.gz	Fastqsanger.gz
	ERR12329510_1.fastq.gz	Fastqsanger.gz
	ERR12329510_2.fastq.gz	Fastqsanger.gz
	ERR12329511_1.fastq.gz	Fastqsanger.gz

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RNA-seq of transplanted Human Intestinal Organoids differentiated with and without PVDF-TrFE Substrate

Project description:Experiment was aimed at testing the compatibility of a piezoelectric material with the differentiation and proper patterning of human intestinal organoids.

2023-12-30 | E-MTAB-13578 | biostudies-arrayexpress

Transplanted Human Intestinal Organoids: A Resource for Modeling Human Intestinal Development

Project description:Transplanted Human Intestinal Organoids: A Resource for Modeling Human Intestinal Development

| PRJNA942271 | ENA

scRNAseq of human iPSC-derived kidney organoids transplanted in the coelomic cavity of chicken embryos compared to untransplanted controls

Project description:Human induced pluripotent stem cell-derived kidney organoids have potential for disease modelling and regenerative medicine purposes. However, they lack a functional vasculature and remain immature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos and then compared them to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq and imaging modalities. We demonstrate vascularization and enhanced maturation of transplanted kidney organoids.

2022-08-05 | E-MTAB-11429 | biostudies-arrayexpress

Transplanted human organoids empower PK/PD assessment of drug candidate for the clinic

Project description:Pharmacokinetic/pharmacodynamic (PK/PD) studies are an essential component of pre-clinical drug discovery. Current best approaches for PK/PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PK/PD studies using transplanted human kidney organoids. We performed PK studies with GFB-887, an investigational new drug now in Phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in human transplanted organoids. Importantly, we established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates, for the first time, feasibility of using transplanted human organoids in PK/PD studies, empowering organoids to revolutionize drug discovery.

2022-06-14 | GSE165104 | GEO

RNA-seq of transplanted pluripotent stem cells-derived human intestinal organoids upon mechanical lengthening and human jejunum tissues

Project description:Human Intestinal Organoids (HIOs) generated from embryonic and/or induced pluripotent stem cell lines offer an avenue to study both developmental and human specific disease states. Recently, progress has been made in scaling and maturing these inherently immature tissues through transplanting them in vivo. However, these resultant grafts best approximate fetal intestinal tissue thus limiting their utility. To induce growth and maturation of HIOs we used a nitinol spring device to mechanically induce enterogenesis of HIO in vivo. HIOs are cultured prior to implantation within the mesentery of immunodeficient mice. They are allowed to grow, vascularize, and mature before a second procedure is performed wherein a compressed nitinol spring is implanted within the lumen of the transplanted HIO (tHIO). Next Generation RNA sequencing was performed across transplanted samples as well as on human surgical samples to highlight the transcriptional similarities and differences between groups. Transcriptionally, the tHIO+S samples were more similar to human tissues than the tHIO. With these initial experiments, we concluded that the application of an intraluminal uniaxial force is a practical method to induce maturation of tHIOs in vivo without concomitant architectural disruptions. While our current system does lack certain complexities, we have demonstrated enterogenesis by means of mechanical manipulation.

2018-03-30 | E-MTAB-6017 | biostudies-arrayexpress

Transretinal migration of astrocytes and brain/spinal cord-like cells arising from subretinally transplanted human retinal organoids

Project description:Subretinal transplantation of human retinal organoid-derived cells can potentially restore vision lost in photoreceptor dystrophies. Prior studies analyzed the maturation, integration, and function of transplanted organoid cells in the subretinal region, but detailed molecular analysis of transplanted photoreceptor and of cells that migrate to other retinal layers has not been conducted. Here, we characterized migratory and non-migratory organoid-derived cells following subretinal transplantation into a dystrophic host. Retinal organoids derived from Crx-tdTomato+ H9 human embryonic stem cells (hESC) (aged D134) were transplanted into immunodeficient Rd1/NS mice. Graft-derived cells using single-cell RNA sequencing and histological analysis were analyzed 4.5 months later. Age-matched human retinal organoids maintained in vitro served as controls. Graft-derived cells migrated to all retinal layers, and underwent long-distance tangential migration. Transcriptomic analysis of transplanted cells identified two cell types not found in cultured controls – PAX2-positive retinal astrocytes, and ARX/NKX2-2/HOXC8-positive brain/spinal cord-like neural precursors. Some migrating cells were proliferative, but overall less proliferation was observed in the transplants than the cultured organoids. Transplanted rod and cone photoreceptors remained in the subretinal space, and were more mature than age-matched photoreceptors in cultured organoids. This study shows that extrinsic signals present in the degenerative subretinal space promote maturation of photoreceptors in transplanted retinal organoids, while also inducing formation of migratory cell populations that are not normally derived from retinal progenitors, either in cultured organoids or in vivo. This has important implications for the design and safety of cell-based therapies for treating photoreceptor dystrophies.

2023-05-10 | GSE197847 | GEO

Maturation and circuit integration of transplanted human cortical organoids

Project description:Maturation and circuit integration of transplanted human cortical organoids

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Maturation and circuit integration of transplanted human cortical organoids

Project description:We show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. Magnetic resonance imaging allows monitoring of post-transplantation organoid growth across multiple stem cell lines and animals, while single nucleus profiling reveals high cell diversity and progression of corticogenesis, as well as the emergence of an activity-dependent transcriptional program in neurons.

2022-07-23 | GSE190815 | GEO

Transplanted human intestinal organoids: a resource for modeling human intestinal development.

Project description:The in vitro differentiation of pluripotent stem cells into human intestinal organoids (HIOs) has served as a powerful means for creating complex three-dimensional intestinal structures. Owing to their diverse cell populations, transplantation into an animal host is supported with this system and allows the temporal formation of fully laminated structures, including crypt-villus architecture and smooth muscle layers that resemble native human intestine. Although the endpoint of HIO engraftment has been well described, here we aim to elucidate the developmental stages of HIO engraftment and establish whether it parallels fetal human intestinal development. We analyzed a time course of transplanted HIOs histologically at 2, 4, 6 and 8 weeks post-transplantation, and demonstrated that HIO maturation closely resembles key stages of fetal human intestinal development. We also utilized single-nuclear RNA sequencing to determine and track the emergence of distinct cell populations over time, and validated our transcriptomic data through in situ protein expression. These observations suggest that transplanted HIOs do indeed recapitulate early intestinal development, solidifying their value as a human intestinal model system.

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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

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