Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell gene expression analysis of X-linked Alport syndrome kidney organoid models and isogenic controls

ABSTRACT: In study we investigated podocyte maturation, with a particular focus on type IV collagen maturation in the glomerular basement membrane (GBM) of kidney organoids over extended culture periods (comparing Control Organoid d22 R2 with Control Organoid d38). The secondary aim was to compare the gene expression profiles of podocytes in X-linked Alport syndrome (XLAS) organoid models with isogenic controls at an early culture time point (day 22). Two distinct batches of sample collection were conducted to capture early and later stages of GBM development. In the first batch, three libraries were generated by collecting 16 organoids from one isogenic control, one severe XLAS model, and one moderate XLAS model on day 22 of differentiation. In the second batch, two libraries were created to evaluate the impact of culture duration on GBM maturation by harvesting an additional isogenic control organoid at both day 22 and day 38 of culture. Organoids were dissociated using a two-step enzymatic and mechanical protocol to obtain single-cell suspensions, with cell viability ranging between 70% and 85%. This experimental design enabled a comparative analysis of GBM maturation dynamics between early and late time points and across different severities of XLAS. Findings from this study provided insights into the cellular mechanisms underlying GBM abnormalities in Alport syndrome and supported the potential for GBM maturation in kidney organoids over time.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281081 | GEO | 2025/07/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Impact of prolonged culture on gene expression profiles of iPSC-derived kidney organoids

Project description:Kidney organoids serve as an invaluable platform for modeling hereditary renal diseases and developing therapeutic interventions. While various kidney organoid differentiation protocols have been developed, the protocol introduced by Morizane et al. was among the first to generate kidney organoids from induced pluripotent stem cells (iPSCs). By using a modified version of this protocol, we successfully generated kidney organoids in 21 days. Most studies on kidney organoids focus on early stages, typically between days 21 and 29, leaving the gene expression dynamics during prolonged culture less explored. In this study, we cultured healthy iPSC-derived kidney organoids for 22, 32, and 42 days and performed bulk RNA sequencing to investigate overall gene expression regulation. Kidney organoids contain over 15 distinct cell types, making them a complex model for studying cell-type-specific maturation. By comparing organoids at early (day 22), mid (day 32), and late (day 42) time points, we observed significant changes in gene expression, particularly in genes related to the extracellular matrix, alongside the downregulation of podocyte-specific genes. Notably, we confirmed the upregulation of podocyte-specific collagen IV genes (COL4A3 and COL4A4), which are critical for forming the glomerular basement membrane (GBM). Overall, these findings underscore the importance of maintaining organoids in culture for at least 15 days beyond the last day of differentiation (day 21) to ensure the development of a more mature GBM, essential for BM disease modeling such as Alport syndrome.

2025-07-29 | GSE281080 | GEO

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoid

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to22 batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-01-31 | PXD023705 | Pride

Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoids

Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.

2022-02-10 | PXD023694 | Pride

RNA-seq of single cholangiocyte-derived organoids reveals high organoid-to-organoid variability

Project description:Organoids have been established from the majority of tissue resident stem cells. In recent years, several reports hinted at intraculture organoid variability, but a systematic analysis of such a heterogeneity has not been performed before. Here, we used RNA-seq of individual organoids to address this question. Importantly, we find that batch-to-batch variation is very low, even when prepared by different researchers. On the other hand, there is organoid-to-organoid variability within a culture. Using differential gene expression, we did not identify specific pathways that drive this variability, pointing towards possible effects of the microenvironment within the culture condition.

2022-08-01 | GSE205753 | GEO

Accelerated and Improved Differentiation of Retinal Organoids from Mouse Pluripotent Stem Cells in Rotating-Wall Bioreactors

Project description:Pluripotent stem cells can be differentiated into three-dimensional (3D) retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall bioreactors (RWB) to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWB demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWB organoids at day (D)25 reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.

2018-01-18 | GSE102727 | GEO

DNA Repair Profiling of HGSC Organoids

Project description:<p>In this study, 34 ovarian tumor organoids generated from 23 patients underwent paired DNA damage repair defect functional analyses and whole exome sequencing analysis to compare genetic mutational status to DNA repair functional capacity. 22 of the patients had high grade serous cancer and 1 of the patients had low grade serous cancer. A normal control, fresh parent tumor, and cells from the organoid culture generated from the parent tumor underwent whole exome sequencing analysis and the data from the sequencing analysis is provided here.</p>

| phs001685 | dbGaP

iPSC-derived type IV collagen α5-expressing kidney organoids model Alport syndrome

Project description:Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS.

2023-07-06 | GSE236314 | GEO

Proteome and secretome analysis of human dorsal forebrain organoids reveals a time-dependent shift in the abundance of cell adhesion and extracellular matrix proteins

Project description:Temporal dynamics of prenatal brain development are influenced by changes in the microenvironment. Particularly, extracellular proteins contribute to the dynamic niche that balances neural stem cell proliferation and differentiation. Here, we present a resource for proteome and secretome analysis of human induced pluripotent stem cell-derived dorsal forebrain organoids over the early developmental period. We used liquid chromatography-mass spectrometry to identify proteins found in whole organoid and secreted proteins at days 20, 35, and 50 of dorsal forebrain organoid differentiation. We show that the whole organoid proteome demonstrates progression in the neurodevelopmental trajectory with reduced proliferation and increased neural differentiation over time. However, secretome analysis revealed a unique signature for developmental progression. Cell adhesion molecules are enriched in the secretome of day 35 organoids, while secretome of day 50 organoids is enriched with extracellular matrix proteins, demonstrating a change in the extracellular interactions over time of organoid differentiation and maturation. We, therefore, show the relevance of secretome analysis for the thorough study of extracellular matrix-related proteins and the importance of time course study of neural organoids to understand the subtle changes that guide human neurodevelopment.

2024-05-27 | MSV000094878 | MassIVE

Whole transcriptome data of human liver organoids cultured in Matrigel and polyisocyanopeptides-based hydrogel

Project description:End-stage liver diseases are an increasing health burden and liver transplantations are currently the only curative treatment option. Due to a lack of donor livers, alternative treatments are urgently needed. Human liver organoids are very promising for regenerative medicine, however, organoids are currently cultured in Matrigel, which is extracted from the extracellular matrix of the Engelbreth-Holm-Swarm mouse sarcoma. Matrigel is poorly defined, suffers from high batch-to-batch variability and is of murine origin, which limits clinical application of organoids. Here, a novel hydrogel based on polyisocyanopeptides (PIC) and laminin-111 is described for human liver organoid culture. PIC is a synthetic hydrogel with thermodynamic properties, making it easy to handle and very attractive for clinical applications. Organoids in an optimized PIC hydrogel proliferate at rates comparable to Matrigel; proliferation rates are stiffness-dependent, with lower stiffnesses being optimal for organoid proliferation. Moreover, organoids can be efficiently differentiated towards hepatocyte-like cells with key liver functions. This proliferation and differentiation potential can be maintained over at least 16 passages. Our results indicate that PIC is a promising material for human liver organoid culture and has the potential to be used in a variety of clinical applications including cell therapy and tissue engineering.

2020-12-23 | GSE143223 | GEO

Large-scale study suggests effects of trisomy 21 on fetal neurodevelopment may be more subtle than variability between organoids and isogenic lines

Project description:This study examines cortical organoids generated from a panel of isogenic trisomic and disomic iPSC lines (subclones) as a model of early fetal brain development in Down syndrome. An initial experiment comparing organoids from one trisomic and one disomic line showed many genome-wide transcriptomic differences and modest differences in cell-type proportions, suggesting there may be a neurodevelopmental phenotype that is due to trisomy of chr 21. To better control for multiple sources of variation, we undertook a highly robust study of ∼1,200 organoids using an expanded panel of six all-isogenic lines, three disomic, and three trisomic. The power of this experimental design was indicated by strong detection of the ∼1.5- fold difference in chr21 genes. However, the numerous expression differences in non-chr21 genes seen in the smaller experiment fell away, and the differences in cell-type representation between lines did not correlate with trisomy 21. Results suggest that the initial smaller experiment picked up differences between small organoid samples and individual isogenic lines, which “averaged out” in the larger panel of isogenic lines. Our results indicate that even when organoid and batch variability are better controlled for, variation between isogenic cell lines (even subclones) may obscure, or be conflated with, subtle neurodevelopmental phenotypes that may be present in ∼2nd trimester DS brain development. Interestingly, despite this variability between organoid batches and lines, and the “fetal stage” of these organoids, an increase in secreted Aβ40 peptide levels—an Alzheimer-related cellular phenotype—was more strongly associated with trisomy 21 status than were neurodevelopmental shifts in cell-type composition.

2023-01-07 | GSE222365 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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