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Related Concept Videos

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Related Experiment Video

Updated: Aug 1, 2025

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Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk

Jiahn Choi1, Xusheng Zhang2, Wenge Li1

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York.

Molecular Cancer Research : MCR
|April 25, 2023
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A Western diet (NWD1) reprograms intestinal stem cells, altering mitochondrial function and promoting tumor development. This highlights how diet influences gut health and cancer risk, mirroring inflammatory bowel disease mechanisms.

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Area of Science:

  • Gastroenterology and Nutrition Science
  • Cancer Biology
  • Stem Cell Biology

Background:

  • The Western diet is linked to increased intestinal cancer risk.
  • Nutritional environments dynamically shape the competition for mucosal maintenance and tumorigenesis.

Purpose of the Study:

  • To investigate how the New Western-style diet 1 (NWD1) affects intestinal stem cells and lineage reprogramming.
  • To understand the molecular mechanisms underlying diet-induced intestinal tumorigenesis.

Main Methods:

  • Utilized a New Western-style diet 1 (NWD1) in mouse models.
  • Employed bulk and single-cell RNA sequencing, single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), functional genomics, and imaging.
  • Performed genetic inactivation of Ppargc1a in Lgr5hi stem cells.

Main Results:

  • NWD1 reprogrammed Lgr5hi stem cells, epigenetically downregulating Ppargc1a and altering mitochondrial function.
  • This reprogramming suppressed stem cell function and progeny maturation, recapitulated by Ppargc1a inactivation.
  • Mobilized Bmi1+, Ascl2hi cells adapted lineages, promoting antigen processing and inflammation, paralleling inflammatory bowel disease mechanisms.
  • Diet-induced stem cell plasticity influences the balance of stem cell populations in colon tumors.

Conclusions:

  • Dietary components significantly impact intestinal stem cell plasticity and function.
  • Nutritional environments play a critical role in shaping the landscape of intestinal tumorigenesis.
  • The findings offer insights into the interplay between diet, stem cell behavior, and cancer development, with implications for inflammatory bowel disease.