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Updated: Oct 7, 2025
06:40
3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
Published on: April 1, 2021
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Adaptive differentiation promotes intestinal villus recovery
Takahiro E Ohara1, Marco Colonna1, Thaddeus S Stappenbeck2
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Developmental Cell
|January 11, 2022
Summary
Severe intestinal damage triggers progenitor cells to adopt a temporary fetal-like state, aiding tissue repair. This "adaptive differentiation" process is crucial for maintaining barrier integrity and promoting villus regeneration.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Gastroenterology
Background:
- Tissue damage and loss of differentiated cells are common in many diseases.
- In high-turnover tissues, understanding repair mechanisms is critical for therapeutic development.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms of tissue repair in high-turnover tissues following severe damage.
- To identify novel cell populations and pathways involved in intestinal regeneration.
Main Methods:
- Acute villus injury model in mice.
- Transcriptional and morphological analysis of progenitor-derived cells.
- Investigation of the role of yes-associated protein (YAP) signaling.
Main Results:
- Identified atrophy-induced villus epithelial cells (aVECs) covering injured villi.
- aVECs exhibit a unique postmitotic state with fetal markers but are differentiated.
- YAP activation in aVECs is essential for maintaining barrier integrity and villus regeneration.
Conclusions:
- Defined a novel repair mechanism termed "adaptive differentiation" in high-turnover tissues.
- Demonstrated that progenitor cells can acquire a fetal-like, differentiated state to facilitate repair.
- Highlighted the critical role of YAP signaling in injury-induced intestinal regeneration.
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