The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist

James R. Goldenring, Ki Taek Nam, Jason C. Mills

Research output: Contribution to journalReview articlepeer-review

68 Citations (Scopus)


The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itself trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.

Original languageEnglish
Pages (from-to)2759-2764
Number of pages6
JournalExperimental Cell Research
Issue number19
Publication statusPublished - 2011 Nov 15

Bibliographical note

Funding Information:
Dr. Goldenring and Dr. Mills have both been supported by the AGA Funderburg Award in Gastric Biology Related to Cancer . Dr. Goldenring is also supported by grants from a Department of Veterans Affairs Merit Review Award, RO1 DK071590 from the National Institutes of Health , and by core resources of the Vanderbilt Digestive Disease Center , P30 DK058404 . Dr. Mills is also supported by DDC-115769 from the American Cancer Society and R01 DK-079798 and P30 DK052574 (the Washington University DDRCC), both from the National Institute of Diabetes and Digestive and Kidney Disease .

All Science Journal Classification (ASJC) codes

  • Cell Biology


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