Studies of intestinal stem cells using normal, chimeric, and transgenic mice ¹

Abstract

The mouse intestinal epithelium represents a continuous developmental system. Its four principal differentiated cell types--enterocytes, goblet, enteroendocrine, and Paneth cells--are derived from a common multipotent stem cell located near the base of monoclonal crypts. Members of these four lineages undergo rapid and perpetual renewal along an anatomically well-defined pathway. The gut epithelium provides a unique mammalian model for studying the biological features of stem cells (e.g., their ability to undergo asymmetric division, their enormous proliferative potential, their capacity for functional anchorage in a niche), examining how stem cell hierarchies are established and maintained in renewing cell populations, analyzing the relationships between passage through the cell cycle and lineage allocation (commitment), and defining the mechanisms that give stem cells a "positional address" along the cephalocaudal axis, allowing them to generate regional differences in the differentiation programs of their derived lineages (axial pattern formation).

Immunohistochemistry of Carbonic Anhydrase Isozyme IX (MN/CA IX) in Human Gut Reveals Polarized Expression in the Epithelial Cells with the Highest Proliferative Capacity

“…Stem cells located in the crypts are a source for continuous and rapid renewal of the epithelium (Gordon 1989). Earlier studies in mice have shown that each small intestinal crypt produces an average of 13-16 new cells/hr (Gordon et al 1992). Cell differentiation and cell migration are coupled events in the gut.…”

“…Cell differentiation and cell migration are coupled events in the gut. The epithelial cells differentiate and mature during migration from the crypt to the apex of the villus or surface epithelial cuff (Lipkin 1985;Gordon 1989;Gordon et al 1992). This process is completed in a few days, which makes the mammalian intestinal epithelium a unique model system for studying cell differentiation.…”

TGF-β1 effects on proliferation of rat intestinal epithelial cells are due to inhibition of cyclin D1 expression

“…Cell proliferation is restricted to a subpopulation of enterocytes located in the crypts at the bases of the villi (Babyatsky and Podolsky, 1991). Mitotic activity ceases as cells migrate out of the crypts, and there is a concomitant increase in the expression of a number of di erentiated gene products (Gordon et al, 1992;Traber, 1994). Di erentiated enterocytes are removed by the process of apoptosis which occurs throughout the villus and by exfoliation which occurs at the villus tip (Gavrieli et al, 1992;Hall et al, 1994;Chandrasekaran et al, 1996).…”

Gata4 Is Essential for the Maintenance of Jejunal-Ileal Identities in the Adult Mouse Small Intestine

“…The mammalian small intestine is lined by a highly specialized epithelium that displays a wide-ranging yet tightly regulated functional diversity along its cephalo-caudal axis (13). The functional diversity is linked to a continuous renewal process in which stem cells located near the base of crypts produce transit-amplifying cells that ultimately differentiate into four principal cell types.…”