Defining Epithelial Cell Progenitors in the Human Oxyntic Mucosa

Abstract

In the human stomach, the oxyntic epithelium includes numerous tubular invaginations consisting of short pits opening into long glands. The pit is lined by pit cells, whereas the gland is composed of three regions: the base, containing zymogenic cells; the neck, containing neck cells; and the isthmus, composed of little known immature cells and of parietal cells, which are also scattered through the neck and base. The aim of this study was to examine the ultrastructure of the immature cells and to determine their relation to mature cells. To do so, normal oxyntic mucosal biopsies from subjects ranging from 20-43 years old were fixed in aldehydes and postfixed in reduced osmium for electron microscopy and morphometric analysis. The immature cells were sorted out into four classes, whose roles were clarified by comparison with the thoroughly investigated mouse oxyntic epithelium. The first class was composed of the least differentiated immature cells, which were rare and characterized by minute, dense, or cored secretory granules and were accordingly named mini-granule cells. Their function was not clarified. The second class consisted of pre-pit cells, which were characterized by few dense mucous granules and give rise to pit cells that ascend the pit wall and, after reaching the luminal surface, die or are extruded. Both pre-pit and pit cells underwent continuous renewal and, therefore, together constituted a renewal system referred to as pit cell lineage. The third class, or pre-neck cells, characterized by cored secretory granules, give rise to neck cells that descend toward the base region and differentiate further into pre-zymogenic cells, which finally become zymogenic cells. The latter eventually degenerate and die. Thus pre-neck cells and their progeny constitute a renewing system, designated zymogenic cell lineage. The fourth class, or pre-parietal cells, characterized by long microvilli and few tubulovesicles, differentiate into parietal cells that descend along the neck and base regions and eventually degenerate and die. Pre-parietal and parietal cells represent a renewing system referred to as parietal cell lineage. While the origin of the last three classes of progenitor cells has not been elucidated, it is likely that they arise either from an unidentified multipotential stem cell, possibly the minigranule cell itself, or from the mitotic activity of pre-pit and pre-neck cells. In conclusion, the human oxyntic epithelium is composed of continually renewing cells organized in distinct cell lineages.

IQGAPs are differentially expressed and regulated in polarized gastric epithelial cells

“…This staining pattern is expected in immature parietal cells (19). The cellular origin of parietal cells has not been definitively established in any species, but these cells have been postulated to arise from pre-neck and pre-pit cell precursors in humans (22). Thus the presence of GSII lectin-staining, mucous-like granules in a subpopulation of parietal cells suggests that these cells are immature and may have pre-neck cell origins.…”

Attributes of adult stem cells

“…There are few markers described for gastric stem cells; however, Bjerknes and Cheng [99] established that multipotential progenitor cells exist in the mouse stomach; using a mutagenicity strategy with ethylnitrosourea, they created mutant clones in adult hemizygous ROSA26 mice in vivo that did not express β-galactosidase, and all cell lineages could be found within a single clone -persuasive evidence for the existence of multipotential cells. From ultrastructural observations in the isthmic region of human stomach, Karam et al [100] have suggested that perhaps the stem cells are so-called mini-granule cells, cells with minute, dense or cored, secretory granules, somewhat akin to the granule-free cells found in the mouse. In the isthmic region of mouse antral glands, a population of LRCs have been found expressing a protein more characteristic of the small intestine, villin [101].…”

Stomach-specific Calpain, nCL-2, Localizes in Mucus Cells and Proteolyzes the β-Subunit of Coatomer Complex, β-COP

“…The pits are lined by pit cells that secrete neutral mucus to protect the epithelium from acid (25). The oxyntic glands in the corpus consist of acid-secreting parietal cells, pepsinogen-secreting chief cells, and hormone-secreting enteroendocrine cells (25,26). Pylorocytes and gastrin-secreting G cells are mainly found in the pyloric glands of the pylorus (27).…”