Generating Patterned Kidney Organoids for Studying Development and Diseases [scRNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA545652 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9165480_1.fastq.gz | Fastqsanger.gz | |||
| SRR9165480_2.fastq.gz | Fastqsanger.gz | |||
| SRR9165476_1.fastq.gz | Fastqsanger.gz | |||
| SRR9165476_2.fastq.gz | Fastqsanger.gz | |||
| SRR9165477_1.fastq.gz | Fastqsanger.gz |
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Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases
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Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases [bulk RNA-Seq]
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Project description:Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening.
2019-06-01 | GSE132023 | GEO
Project description:Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening.
2019-05-29 | GSE131841 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-06-01 | GSE132026 | GEO
Project description:Studying the physiology and pathology of gastrointestinal (GI) tissues requires tools that can accurately mimic their complex architecture and functionality in vitro. Organoids have emerged as one such promising tool, though their closed structures with poorly accessible lumen and limited observability makes readouts challenging. In this study, we introduce a bioengineered organoid platform that generates bilaterally accessible 3D tissue models, allowing independent manipulation of both the apical and basal sides of patterned epithelial monolayers. We successfully constructed gastric, small intestinal, caecal, and colonic epithelial models that faithfully reproduced tissue-respective geometries and exhibited high physiological relevance, evidenced by the regionalization of stem cells and transcriptional resemblance to real epithelia. The gained observability allowed single-cell tracking over time and studies into the motility of cells in immersion and air-liquid interface cultures. Additionally, this model recapitulated Trichuris muris infection of the caecum epithelium, allowing the first live imaging of syncytial tunnel formation. Overall, this platform offers accessible organoids with improved observability, making it a valuable tool for investigating the dynamics of GI epithelial cells and their interactions with pathogens.
2023-08-21 | GSE241012 | GEO
Project description:Loss of contractility and acquisition of an epithelial phenotype of vascular smooth muscle cells (VSMCs) are key events in proliferative vascular pathologies such as atherosclerosis and post-angioplastic restenosis. There is no proper cell culture system allowing VSMC differentiation so that it is difficult to delineate the molecular mechanism responsible for proliferative vasculopathy. We investigated whether a micro-patterned substrate could restore the contractile phenotype of VSMCs in vitro. To induce and maintain the differentiated VSMC phenotype in vitro, we introduced a micro-patterned groove substrate to modulate the morphology and function of VSMCs.
2013-11-14 | E-MTAB-1888 | biostudies-arrayexpress
Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.
2022-05-04 | GSE179597 | GEO
Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.
2022-05-04 | GSE179599 | GEO
Project description:Immortal spheroids were generated from fetal mouse intestine using the culture system developed to culture organoids from adult intestinal epithelium. Spheroids are made of a monostratified polarized epithelium displaying a poorly differentiated intestinal phenotype. The proportion of spheroids generated from intestinal explants progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Spheroid cells show indefinite self-renewing properties but exhibit a transcriptome strikingly different from that of adult intestinal stem cells reminiscent of incompletely caudalized progenitors. The receptor Lgr4, but not Lgr5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two markers highly enriched in spheroids, are expressed throughout the E14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroid-generating cells as developmental progenitors involved in generation of the prenatal intestinal epithelium. Ex vivo, spheroid cells have the potential to differentiate into organoids, thus qualifying them as a new type of intestinal stem-like cells. Two-channel microarray experiments were performed from spheroid/organoid pairs isolated each from a given embryo. Following initial seeding of small intestine from a given embryo/mouse (at E16, E18 or P0), spheroids and organoids were selectively picked up for each animal and replated for 3 passages to reach sample homogeneity. Hybridization was performed on the 4 independent pairs with dye-swap.
2014-01-21 | E-GEOD-49803 | biostudies-arrayexpress