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DNA methylation analysis validates organoids as a viable model for studying human intestinal aging

ABSTRACT: DNA methylation analysis validates organoids as a viable model for studying human intestinal aging

PROVIDER: PRJNA592962 | ENA |

REPOSITORIES: ENA

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DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (methylation)

Project description:DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (methylation)

| PRJNA592968 | ENA

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (expression)

Project description:DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (expression)

| PRJNA592967 | ENA

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (expression)

Project description:The epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. While the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be utilized for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. Here we test whether stem cell enriched organoids preserve the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived. To address this, we use standard human methylation arrays and the human 'epigenetic clock' as a biomarker of age to analyze in vitro derived three-dimensional stem cell-enriched intestinal organoids. We find that human stem cell-enriched spheroids maintain segmental differences in methylation patterns and that age, as measured by the epigenetic clock, is largely maintained in spheroids. Surprisingly, we find that small intestine spheroids exhibit striking epigenetic age reduction relative to colon spheroids.

2019-12-03 | GSE141255 | GEO

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (methylation)

2019-12-03 | GSE141254 | GEO

DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.

Project description:BACKGROUND & AIMS:The epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived. METHODS:To address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids. RESULTS:We found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon. CONCLUSIONS:Our data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro.

| S-EPMC7044532 | biostudies-literature

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-03 | GSE141256 | GEO

Lipid Profiling of Mouse Intestinal Organoids for studying APC Mutations

Project description:Inactivating mutations including both germline and somatic mutations in the adenomatous polyposis coli (APC) gene drives most familial and sporadic colorectal cancers. Understanding the metabolic implications of this mutation will aid to establish its wider impact on cellular behaviour and potentially inform clinical decisions. However, to date, alterations in lipid metabolism induced by APC mutations remain unclear. Intestinal organoids have gained widespread popularity in studying colorectal cancer and chemotherapies, because their three-dimensional structure more accurately mimics an in vivo environment. Here, we aimed to investigate intra-cellular lipid disturbances induced by APC gene mutations in intestinal organoids using a reversed-phase ultra-high-performance liquid chromatography mass spectrometry (RP-UHPLC-MS)-based lipid profiling method. Lipids of the organoids grown from either wildtype (WT) or mice with Apc mutations (Lgr5–EGFP-IRES-CreERT2 Apcfl/fl) were extracted and analysed using RP-UHPLC-MS. Concentrations of phospholipids (e.g. PC(16:0/16:0), PC(18:1/20:0), PC(38:0), PC(18:1/22:1)), ceramides (e.g. Cer(d18:0/22:0), Cer(d42:0), Cer(d18:1/24:1)) and hexosylceramide (e.g. HexCer(d18:1/16:0), HexCer(d18:1/22:0)) were higher in Apcfl/fl organoids, whereas levels of sphingomyelins (e.g. SM(d18:1/14:0), SM(d18:1/16:0) ) were lower compared to WT. These observations indicate that cellular metabolism of sphingomyelin was upregulated, resulting in the cellular accumulation of ceramides and production of HexCer due to the absence of Apcfl/fl in the organoids. Our observations demonstrated lipid profiling of organoids and provided an enhanced insight into the effects of the APC mutations on lipid metabolism, making for a valuable addition to screening options of the organoid lipidome.

2021-02-17 | ST001707 | MetabolomicsWorkbench

Generating Patterned Kidney Organoids for Studying Development and Diseases

Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases

| PRJNA545689 | ENA

Generation of intestinal organoids from human urine cells

Project description:Intestinal organoids are ideal models for studying human intestinal diseases. We report functional intestinal organoid models (U-iIOs) generated by reprogramming human urinary epithelial cells (hUCs). RNA-seq reveals the intestinal lineage identity of U-iIOs.

2024-07-07 | GSE230718 | GEO

Generating Patterned Kidney Organoids for Studying Development and Diseases [scRNA-Seq]

Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases [scRNA-Seq]

| PRJNA545652 | ENA