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Related Concept Videos

Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Related Experiment Video

Updated: Jul 6, 2025

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity.

Ryan C Zitter1, Rishi Man Chugh1, Payel Bhanja1

  • 1Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Cells
|January 11, 2024
PubMed
Summary

Male intestines show higher radiosensitivity and oxidative stress compared to females, irrespective of sex hormones. This sex-specific difference in intestinal radiosensitivity was observed in both mouse models and patient-derived organoids, suggesting a potential mechanism for varied radiation therapy outcomes.

Keywords:
ISCsLGR5+oxidative stressradiosensitivity

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Area of Science:

  • Radiation Oncology
  • Gastrointestinal Malignancy
  • Cell Biology

Background:

  • Tissue radiosensitivity is crucial for radiation therapy outcomes.
  • Intestinal radiosensitivity presents a challenge in treating gastrointestinal malignancies.
  • Existing clinical data suggest potential sex-based differences in radiotherapy response.

Purpose of the Study:

  • To investigate sex-specific differences in intestinal epithelial radiosensitivity.
  • To explore potential mechanisms underlying these sex-specific differences.

Main Methods:

  • Abdominal irradiation in a mouse model.
  • Assessment of oxidative stress and injury in male and female mice.
  • Ex vivo studies using patient-derived intestinal organoids (PID).
  • Transcriptomic analysis of human intestinal stem cells.

Main Results:

  • Male mice exhibited significantly higher oxidative stress and intestinal injury post-irradiation compared to females.
  • Lgr5+ intestinal stem cells from male mice demonstrated increased sensitivity to radiation-induced toxicity.
  • Sex-specific radiosensitivity differences persisted in pre-pubescent mice, indicating independence from sex hormones.
  • Male patient-derived intestinal organoids showed greater radiation sensitivity, evidenced by crypt loss, reduced size, and compromised membrane integrity.

Conclusions:

  • Significant sex-specific differences exist in intestinal radiosensitivity, with males being more sensitive.
  • These differences are not mediated by sex hormones.
  • Upregulation of mitochondrial oxidative metabolism in male intestinal stem cells may underlie increased radiosensitivity.