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

65 Scopus citations


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
StatePublished - Nov 15 2011


  • Chief cell
  • Gastric adenocarcinoma
  • Intestinal metaplasia
  • Metaplasia
  • SPEM
  • Transdifferentiation
  • Zymogenic cell


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