Residual embryonic cells as precursors of a Barrett's-like metaplasia

Xia Wang; Hong Ouyang; Yusuke Yamamoto; Pooja Ashok Kumar; Tay Seok Wei; Rania Dagher; Matthew Vincent; Xin Lu; Andrew M Bellizzi; Khek Yu Ho; Christopher P Crum; Wa Xian; Frank McKeon

doi:10.1016/j.cell.2011.05.026

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Residual embryonic cells as precursors of a Barrett's-like metaplasia

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Residual embryonic cells as precursors of a Barrett's-like metaplasia

Xia Wang, Hong Ouyang, Yusuke Yamamoto, Pooja Ashok Kumar, Tay Seok Wei, Rania Dagher, Matthew Vincent, Xin Lu, Andrew M Bellizzi, Khek Yu Ho, …

Cell (Cambridge), Vol.145(7), pp.1023-1035

06/24/2011

DOI: 10.1016/j.cell.2011.05.026

PMCID: PMC3125107

PMID: 21703447

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Abstract

Barrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Triggered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embryonic epithelium that is normally undermined and replaced by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squamocolumnar junction, the source of Barrett's metaplasia. We show that upon programmed damage to the squamous epithelium, these embryonic cells migrate toward adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity.

Humans

Gene Expression Profiling

Phosphoproteins - genetics

Phosphoproteins - metabolism

Metaplasia

Esophagus - pathology

Animals

Barrett Esophagus - pathology

Intestine, Small - cytology

Barrett Esophagus - embryology

Trans-Activators - genetics

Trans-Activators - metabolism

Mice

Details

Title: Subtitle: Residual embryonic cells as precursors of a Barrett's-like metaplasia
Creators: Xia Wang - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Hong Ouyang
Yusuke Yamamoto
Pooja Ashok Kumar
Tay Seok Wei
Rania Dagher
Matthew Vincent
Xin Lu
Andrew M Bellizzi
Khek Yu Ho
Christopher P Crum
Wa Xian
Frank McKeon
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.145(7), pp.1023-1035
Publisher: United States
DOI: 10.1016/j.cell.2011.05.026
PMID: 21703447
PMCID: PMC3125107
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: R21CA124688 / NCI NIH HHS R01-GM083348 / NIGMS NIH HHS R01 GM083348 / NIGMS NIH HHS R01 GM083348-04 / NIGMS NIH HHS R21 CA124688-02S1 / NCI NIH HHS R21 CA124688 / NCI NIH HHS
Language: English
Date published: 06/24/2011
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984047892202771

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