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IPMK-deficient mouse colonic epithelial cell upon DSS-induced acute colitis

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Dataset overview

Participants 6
Samples 6
Reuse readiness 5.6/10 evidence-backed score

Gut Epithelial Inositol Polyphosphate Multikinase Alleviates Experimental Colitis via Governing Tuft Cell Homeostasis.

Park SE, Lee D, Jeong JW, Lee SH, Park SJ, Ryu J, Oh SK, Yang H, et al. · Cellular and molecular gastroenterology and hepatology · 2022

Abstract

<h4>Background & aims</h4>Inositol polyphosphate multikinase (IPMK), an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. Recent studies have identified single-nucleotide polymorphisms in the IPMK gene associated with inflammatory bowel disease predisposition. Therefore, we aimed to investigate the functional significance of IPMK in gut epithelium.<h4>Methods</h4>We generated intestinal epithelial cell (IEC)-specific Ipmk knockout (IPMK<sup>ΔIEC</sup>) mice, and assessed their vulnerability against dextran sulfate sodium-induced experimental colitis. Both bulk and single-cell RNA sequencing were performed to analyze IPMK-deficient colonic epithelial cells and colonic tuft cells.<h4>Results</h4>Although IPMK<sup>ΔIEC</sup> mice developed normally and showed no intestinal abnormalities during homeostasis, Ipmk deletion aggravated dextran sulfate sodium-induced colitis, with higher clinical colitis scores, and increased epithelial barrier permeability. Surprisingly, Ipmk deletion led to a significant decrease in the number of tuft cells without influencing other IECs. Single-cell RNA sequencing of mouse colonic tuft cells showed 3 distinct populations of tuft cells, and further showed that a transcriptionally inactive population was expanded markedly in IPMK<sup>ΔIEC</sup> mice, while neuronal-related cells were relatively decreased.<h4>Conclusions</h4>Cholinergic output from tuft cells is known to be critical for the restoration of intestinal architecture upon damage, supporting that tuft cell-defective IPMK<sup>ΔIEC</sup> mice are more prone to colitis. Thus, intestinal epithelial IPMK is a critical regulator of colonic integrity and tissue regeneration by determining tuft cell homeostasis and affecting cholinergic output.

doi:10.1016/j.jcmgh.2022.08.004 ↗ PMID 35988719 ↗ PMC9579329 ↗

Study facts

Organism
—
Platform
MGISEQ-2000RS
Age group
adult
Disease groups
—
Anatomical sites
—

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Participant counts are documented
  • Sample counts are documented

Limitations

  • Not documented: feature/otu tables are advertised
  • Not documented: taxonomic tables are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.paired_end True
Sequencing of the prepared DNA nanoball was conducted using the MGIseq system (MGI) with 100-bp paired-end reads.

Section Materials and Methods; mRNA Sequencing and Data Processing, offset 47000
assay.platform MGISEQ-2000RS from source
ENA instrument_model=MGISEQ-2000RS

Section ENA study report, offset —
assay.read_length 100
with 100-bp paired-end reads

Section Materials and Methods; mRNA Sequencing and Data Processing, offset 47000

Cohort

FieldValueEvidence
cohort.age_group adult inferred
Eight- to 22-week-old mice (both male and female) were used in this study.

Section Materials and Methods; Mice, offset 39000
cohort.disease_activity_metadata_available True
Transcriptomic analysis of colonic epithelial cells at an earlier colitis phase

Section Results; transcriptomic analysis of colonic epithelial cells, offset 11000
cohort.study_design cross_sectional inferred
Mice were killed on day 8 for RNA sequencing of colonic epithelial cells (n = 3, 3 per genotype).

Section Results; transcriptomic analysis of colonic epithelial cells, offset 11000
cohort.total_participants 6
Mice were killed on day 8 for RNA sequencing of colonic epithelial cells (n = 3, 3 per genotype).

Section Results; transcriptomic analysis of colonic epithelial cells, offset 11000
cohort.treatment_response_metadata_available True inferred
IPMK ΔIEC mice showed significantly attenuated recovery from colitis.

Section Results; IPMK Deficiency in Colonic Epithelium Exacerbates Experimental Colitis and Attenuates Recovery, offset 6000

Data_Assets

FieldValueEvidence
data_assets.open_access True
"isOpenAccess": "Y"

Section publication metadata, offset 700
data_assets.pipeline_or_tool_versions True
Skewer version 0.2.2 ... STAR version 2.5 ... RSEM version 1.3.0

Section Materials and Methods; mRNA Sequencing and Data Processing, offset 47500
data_assets.qc_or_negative_controls_reported True
raw quality bases in the raw reads were trimmed by Skewer version 0.2.2. The cleaned high-quality reads were mapped

Section Materials and Methods; mRNA Sequencing and Data Processing, offset 47500
data_assets.raw_reads True
The RNA sequencing data were deposited at the National Center for Biotechnology Information Sequence Read Archive. Accession number: PRJNA823796

Section Data Availability Statement, offset 59000

Specimens

FieldValueEvidence
specimens.body_site colon
comparing colonic epithelial cells in DSS-induced acute colitis

Section study description, offset 55
specimens.inflamed_status_available True
colonic epithelial cells at an earlier colitis phase

Section Results; transcriptomic analysis of colonic epithelial cells, offset 11000
specimens.number_of_samples 6 from source
ENA sample_count=6

Section ENA study report, offset —