Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq of small intestinal organoids treated with IL-13 for 0, 1, 4 8 and 24 hours and with the BMP signaling inhibitor DMH1

ABSTRACT: The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. The changes in cellular composition is driven by immune cell derived cytokines. Here we investigate the response over time upon stimulation with 10 ng/mL of the cytokine Interleukin-13 (IL-13). The intestinal organoids were lyzed 48 hours after splitting and IL-13 was added 24h, 8h, 4h and 1h before lysis. Furthermore, we have found BMP signaling to be important in regulating the cellular differentiation induced by IL-13. We therefore added added a combination treatment with the activin receptor-like kinase 2 (ALK-2) signaling inhibitor Dorsomorphin homolog 1 (DMH1) in concentration of 5 uM in some samples 24 hours before lysis. We find that ALK-2 signaling is crucial for IL-13 driven Tuft cell differentiation.

ORGANISM(S): Mus musculus

SUBMITTER: Håvard Lindholm 

PROVIDER: E-MTAB-10455 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13-driven tuft cell hyperplasia.

Lindholm Håvard T HT   Parmar Naveen N   Drurey Claire C   Campillo Poveda Marta M   Vornewald Pia M PM   Ostrop Jenny J   Díez-Sanchez Alberto A   Maizels Rick M RM   Oudhoff Menno J MJ  

Science immunology 20220513 71

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo inf  ...[more]

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