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

Exp Cell Res. 2011 Nov 15;317(19):2759-64. doi: 10.1016/j.yexcr.2011.08.017. Epub 2011 Aug 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adult
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Carcinoma / etiology
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Cell Transdifferentiation / genetics
  • Cell Transdifferentiation / physiology
  • Chief Cells, Gastric / metabolism
  • Chief Cells, Gastric / pathology
  • Chief Cells, Gastric / physiology*
  • Gastric Mucosa / metabolism
  • Humans
  • Metaplasia
  • Precancerous Conditions / etiology*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Stomach / pathology*
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology


  • BHLHA15 protein, human
  • Basic Helix-Loop-Helix Transcription Factors