Project description:Development of intestinal organoids from single intestinal stem cells is driven by the regenerative capacity of the intestinal epithelium. To unravel molecular mechanisms orchestrating organoid formation and self-organization, we developed a high-content image-based screening assay for an annotated compound library. We generated multivariate feature profiles for hundreds of thousands of individual organoids to quantitatively describe the phenotypic landscape of organoid development. Generated phenotypic fingerprints were then used to infer regulatory genetic interactions from a single screen, establishing a novel paradigm in genetic interaction screening applied to an emergent system. This allowed the identification of novel modules of genes that regulate cell identity transitions and maintain the balance between regeneration and homeostasis. We then characterized a crucial role of retinoic acid nuclear receptors in controlling the exit from the regenerative state and in driving enterocyte differentiation. By combining quantitative imaging with RNA sequencing we confirmed the role of endogenous retinoic acid signaling and metabolism in initiating transcriptional programs guiding intestinal epithelium cell fate transitions and identified a small molecule inhibitor of retinoid x receptor, RXR, that improved intestinal regeneration in vivo. We use RNA sequencing to describe transcriptional changes induced in intestinal organoids cultured in presence of retinoic signaling modulators.

2020-05-22 | GSE134755 | GEO

Regenerative landscape of intestinal organoids (scRNA-Seq)

Project description:We use RNA sequencing to describe transcriptional changes induced in intestinal organoids cultured in presence of retinoic signaling modulators

2020-05-22 | GSE147135 | GEO

Regenerative landscape of intestinal organoids (bulk RNA-Seq 2)

Project description:We use RNA sequencing to describe transcriptional changes induced in intestinal organoids cultured in presence of retinoic signaling modulators

2020-05-22 | GSE147134 | GEO

Genome-wide analysis of the transcriptional and alternative splicing landscape in intestinal organoids undergoing nutrient starvation or ER stress

Project description:Our study represents the first detailed analysis of the transcriptional and alternative splicing landscape of intestinal organoids undergoing stress, with biologic replicates, generated by RNA-seq technology. We report significant changes in the expression of genes involved in inflammation, proliferation and transcription, among others. Splicing events commonly regulated by both stresses affected genes regulating splicing and were associated with nonsense-mediated decay (NMD), suggesting that splicing is modulated by an auto-regulatory feedback loop during stress. Murine intestinal organoids were stimulated in triplicate with conditions for either ER stress or nutrient starvation and RNA-seq was conducted to analyze global changes in both gene expression at the transcriptional level and alternative splicing

2016-08-15 | E-GEOD-84989 | biostudies-arrayexpress

Murine intestinal organoids resemble intestinal epithelium in their microRNA profiles

Project description:To compare miRNA expression profiles between freshly isolated intestinal epithelial cells and cultured organoids in mice. Intestinal organoids largely resembled intestinal epithelial cells in their miRNA profiles. Although the expression levels of some miRNAs were different between crypt and villus epithelial cells, such expression patterns were not reproduced during the maturation of intestinal organoids.

2018-05-25 | GSE99237 | GEO

RNA-seq of small intestinal organoids treated with an inhibitor for the epigenetic modifier LSD1

Project description:To assess the role of LSD1 in mice small intestinal epithelium, small intestinal organoids were treated with an inhibitor for LSD1 (GSK-LSD1) and compared to untreated organoids. Similar to intestinal epithelium from mice with an intestinal epithelium specific LSD1-KO, paneth cells dissappear upon GSK-LSD1 treatment. We used these sequencing data to show that these small intestinal organoids have a similar phenotype as mice epithelium without LSD1.

2020-11-16 | E-MTAB-9077 | biostudies-arrayexpress

Expression data from intestinal organoids altered for Tgfbeta signaling

Project description:We treated intestinal organoids continuously for 5 days with or without TgfbR1/2 inhibitor (LY2109761) or Tgfb1 ligand Organoids were continuously treated for 5 days, then RNA was extracted and hybridized to Affymetrix Mouse Genome 430 2.0

2014-06-09 | E-GEOD-58296 | biostudies-arrayexpress

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