Streaming organism.

Abstract

The cell kinetic characteristic of all epithelia is the same. All are analogs of the crypt-villus unit of the gastrointestinal mucosa. Each unit is nourished by at least one determined uncommitted stem cell (DS). When the DS divides, one of its progeny replaces the parent and remains a DS, while the other starts streaming outward. When entering a differentiation pathway it is called a committed stem cell (CS). Cells in the unit differentiate while streaming. Initially they continue multiplying and are called amplifying progenitors (P-cells), then they lose the capacity to synthesize DNA and become non-dividing (quiescent) end cells (Q-cells). All cells except the DS are transitional and short lived (in the crypt they live several days): only the DS is permanent. Since epithelial tissues are cell kinetic analogs of the crypt, it is assumed here that their neoplastic progression is analogous with the adenoma-carcinoma sequence of the crypt. Neoplasia starts when a normal cell is transformed into a neoplastic. If a transitional cell is hit by a carcinogen and transformed into a neoplastic, it soon will be washed out from the system. Only a transformed DS can maintain the neoplastic trait since it never leaves the crypt. Neoplasia is thus a pathology of the DS. There are two differentiation scales in the embryo: global and local. The first starts with the fertilized ovum that divides into stem cells that become more and more determined. Following gastrulation each determined stem cell generates its local progeny of transitional cells that make the tissue units. Determined stem cells are direct descendants of the fertilized ovum, while their transitional progenitors are direct descendants of determined stem cells.