Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing cells in developing rat fundic glands

Abstract

The ontogeny of pepsinogen C-producing cells in rat fundic glands was studied by means of light and electron microscopy using an antiserum raised against a synthetic peptide based on rat pepsinogen C. To confirm the immunocytochemistry results, the expression of rat pepsinogen C messenger RNA (mRNA) in the fundic gland was also examined by in situ hybridization using a digoxigenin-labeled RNA probe. In adult rats, pepsinogen C was produced by chief cells, mucous neck cells, and intermediate mucopeptic cells. Pepsinogen C-producing cells appeared in embryos as early as 18.5 days' gestation. The development of these cells could be classified into four stages: (1) 18.5 days' gestation to 0.5 days after birth; (2) 0.5 days to 2 weeks after birth; (3) 3-4 weeks after birth; (4) 4-8 weeks after birth. In embryos and young animals, pepsinogen C-producing cells were mucopeptic cells. By 4 weeks after birth, mucous neck cells could be distinguished morphologically. The maturation stages of the chief cells could be traced by electron microscopy along the longitudinal axis of the rat fundic gland by double-staining with anti-pepsinogen C antibody and periodic acid-thiocarbohydrazide-silver proteinate. Positive reactions for pepsinogen C and pepsinogen C mRNA expression were detected in mucous neck cells. Therefore, we conclude that mucous neck cells are precursor cells of chief cells. Mucous neck cells, intermediate cells, and chief cells are in the same differentiating cell lineage.

The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1

“…These studies indicated that ZCs arise from mucous neck cell precursors (Suzuki et al, 1983;Karam and Leblond, 1993c;Ge et al, 1998). However, before the current study, no gene required for any step in the differentiation of neck cells into mature, basal ZCs had been identified.…”

“…Morphological studies (Suzuki et al, 1983;Karam and Leblond, 1993c;Ge et al, 1998) suggest that ZCs arise from mucous neck cells that migrate into the base zone. However, this neck-to-ZC transition hypothesis has been recently called into question (Hanby et al, 1999).…”

The Transcription Factor MIST1 Is a Novel Human Gastric Chief Cell Marker Whose Expression Is Lost in Metaplasia, Dysplasia, and Carcinoma

“…Chief cells are digestive-enzyme producing secretory factories that develop from mucous neck cells without an intermediate proliferating progenitor and have therefore generally been considered postmitotic and terminally differentiated. 28,32,74 Despite progress in pyloric epithelial dynamics, 75 in human oxyntic mucosa, all proliferation is thought to derive from stem cells in the isthmus as opposed to the base where chief cells reside. 76 Possibly the most important reason for chief cell neglect is the lack of reliable human chief cell markers that would allow study of their differentiation during metaplasia and neoplasia.…”

Pepsinogen C Expression in Intestinal IEC-6 Cells

“…Studies using in situ hybridisation and PGC immunocytochemistry have shown widespread localisation of PGC mRNA in the gastro-duodenal mucosa of normal rats [3,4]. Particularly strong signals were reported in the rat zymogen and mucous neck cells of the oxyntic glands, and weaker signals in the cardiac and pyloric glands.…”