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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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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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Adult Stem Cells01:33

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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Nucleotide Excision Repair01:38

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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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DNA Damage can Stall the Cell Cycle02:37

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Updated: Jun 11, 2025

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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Age-Dependent Differences in Radiation-Induced DNA Damage Responses in Intestinal Stem Cells.

Guanyu Zhou1, Tsutomu Shimura2, Taiki Yoneima3

  • 1Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 754-8553, Japan.

International Journal of Molecular Sciences
|September 28, 2024
PubMed
Summary
This summary is machine-generated.

Radiation exposure impacts cancer risk differently based on age. This study reveals distinct DNA damage responses in infant versus adult mouse intestinal stem cells, influencing radiation carcinogenesis susceptibility.

Keywords:
DNA damage responseDNA repairLgr5+ intestinal stem cellsage at exposureapoptosiscell cyclegene expression variabilityintestinal cryptsp53 activationradiationstem cell

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Radiation Oncology

Background:

  • Age at exposure significantly modifies radiation-induced cancer risk.
  • Understanding age-related differences in radiation carcinogenesis is crucial but poorly understood.

Purpose of the Study:

  • To compare radiation-induced DNA damage responses in Lgr5+ and Lgr5- intestinal stem cells between infant and adult mice.
  • To elucidate the mechanisms underlying age-dependent susceptibility to radiation carcinogenesis.

Main Methods:

  • Utilized Lgr5-eGFP-ires-Cre mice for stem cell tracking.
  • Performed three-dimensional immunostaining and RNA sequencing.
  • Analyzed apoptosis, mitotic index, and p53 activation post-irradiation.

Main Results:

  • Radiation induced apoptosis and mitotic index more efficiently in adult Lgr5- stem cells than Lgr5+ stem cells.
  • Infant intestinal stem cells showed similar responses regardless of Lgr5 expression.
  • Adult stem cells exhibited rapid p53 activation and greater gene expression variability, with enriched cell cycle and DNA repair pathways post-irradiation.

Conclusions:

  • Radiation-induced DNA damage responses in mouse intestinal crypts differ significantly between infants and adults.
  • These age-dependent differences in stem cell response may explain varying susceptibility to radiation-induced cancer.
  • Findings highlight critical developmental windows in radiation response.