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Related Concept Videos

Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
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Transcriptomic Response to Calcium in Normal Colon Organoids is Impacted by Colon Location and Sex.

Matthew A M Devall1, Christopher H Dampier1, Stephen Eaton1

  • 1Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.

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Summary

Calcium supplementation may protect against colorectal cancer by altering cell composition and gene expression in colon organoids. These effects vary by colon location and sex, potentially interacting with genetic risk factors.

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Area of Science:

  • Gastroenterology and Hepatology
  • Cancer Biology
  • Nutritional Science

Background:

  • Observational studies suggest calcium supplementation may reduce colorectal cancer (CRC) risk.
  • Previous research indicates potential differences in this protective effect based on CRC subsite and sex.
  • Experimental validation of these hypotheses has been challenging.

Purpose of the Study:

  • To investigate the molecular mechanisms by which calcium supplementation influences colon cell composition and gene expression.
  • To explore whether the effects of calcium differ based on colon subsite (right vs. left) and sex.
  • To identify potential overlaps between calcium's effects and genetic factors influencing CRC risk.

Main Methods:

  • Utilized 36 patient-derived normal colon organoid lines from diverse sexes and colon locations.
  • Exposed organoids to varying calcium concentrations (1.66 and 5.0 mmol/L) for 72 hours.
  • Performed bulk RNA-sequencing, cell composition deconvolution (CIBERSORTx), and differential gene expression analysis (DESeq2).
  • Validated findings for specific genes (e.g., HSD17B2) using quantitative PCR (qPCR).

Main Results:

  • High calcium exposure altered cell composition, increasing goblet cells and decreasing stem cells (P < 0.05).
  • Differential gene expression was observed in 485 genes (FDR < 0.05) with higher calcium levels.
  • Forty differentially expressed genes mapped to CRC genome-wide association study loci, suggesting a link to inherited risk.
  • More significant gene expression changes were noted in organoids from the right colon and male subjects compared to the left colon and female subjects.
  • A stronger right-sided effect was confirmed for HSD17B2.

Conclusions:

  • Calcium supplementation influences colon cell differentiation and gene expression, potentially contributing to chemoprevention.
  • The impact of calcium varies by colon location and sex, highlighting the need for personalized approaches.
  • Findings suggest an interaction between nutritional factors (calcium) and genetic predisposition in colorectal cancer development.