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Analysis of transcriptomes in intestinal stem cells in response to Interferon gamma

UID: 11176

Author(s): Hanash, Alan*, Takashima, Shuichiro* * MSK affiliated

Description
Summary from GEO:

"There is limited understanding of how immune-mediated damage impacts intestinal stem cells (ISCs). We found that stem cell compartment injury is a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing ISCs and impairing their recovery in T-cell-mediated injury models. Modeling with ex vivo epithelial cultures indicated ISC depletion and impaired human as well as murine organoid survival upon co-culture with activated T cells, and screening of effector pathways identified Interferon-γ (IFNγ) as a principal mediator of ISC compartment damage. Flow cytometry analysis confirmed expression of IFNγ receptor on ISCs. To investigate if the receptor was functional, we performed transcriptome analysis of ISCs treated with IFNγ. In brief, mRNA profiles of sorted Lgr5-high cells treated with/without IFNγ were generated by deep sequencing, in triplicate, using the TruSeq SBS Kit V4 (Illumina). RNA profiles confirmed a robust IFNγ transcriptional signature in the stem cells, as several IFNγ-related genes were upregulated shortly after exposure, indicating direct activity of IFNγ in ISCs. Epithelial cultures with IFNγ-receptor-deficient ISCs and purified stem cell colonies also indicated direct targeting of the ISCs. This study showed that dysregulated T cell activation and Interferon-γ production are potent mediators of ISC injury."

Overall design from GEO:

"mRNA profiles of isolated Lgr5-high intestinal stem cells treated w/wo interferon gamma were generated by deep sequencing, in triplicate, using the TruSeq SBS Kit V4(Illumina)."
Subject of Study
Mus musculus
Subject(s)
Epithelial Cells
MicroRNAs
Stem Cells
T-Lymphocytes
Transcriptome
Access via GEO


Accession #: GSE139813

Access via BioProject


Accession #: PRJNA587082

Access via SRA


Accession #: SRP227928

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus. BioProject, and SRA databases provide open access to these files.
Associated Publications
Takashima S, Martin M, Jansen S, Fu Y, Bos J, Chandra D, O'Connor M, Mertelsmann A, Vinci P, Kuttiyara J, Devlin S, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer N, Cheng E, Levine R, Liu C, Kolesnick R, Lindemans C, Hanash A. T cell-derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Science Immunology. 2019; 4(42):eaay8556.
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Dataset Format(s)
TXT
Dataset Size
762.1 KB
Data Catalog Record Updated
2024-02-27