Competitive interactions between cells: death, growth, and geography

Abstract

Competitive interactions between cells are the basis of many homeostatic processes in biology. Some of the best-described cases of competition between cells occur in Drosophila: cell competition, whereby somatic cells within a growing epithelium compete with one another for contribution to the adult, and stem cell competition, in which germline or somatic stem cells vie for residency in the niche. Both types of competition are conserved physiological processes, with much to tell us about how cellular neighborhoods influence cell behavior, and have importance to stem cell biology, regeneration and transplantation, and cancer.

Fig. 1

A model of cell competition. (A) Neighboring epithelial cells recognize relative differences in ribosome function through a sensing mechanism that may involve the production of secreted factors by each cell (orange and green dots). (B) Once a difference is sensed, cells acquire “winner” or “loser” status, determined by their relative ribosome function. Loser cells sense stress and activate the JNK signaling pathway and expression of the proapoptotic factor, Hid. Hid induces apoptosis and leads to loser-cell death. Winner cells, with optimal ribosome function, are stimulated to proliferate faster. They also can activate genes required for cell engulfment, leading them to engulf dying loser cells (asterisk). Arrows depict genetic relationships rather than direct biochemical interactions.

Fig. 2

Cells are insulated from competition by compartment boundaries. (A) Cell competition occurring on one side (left) of a compartment boundary (dotted line) does not affect cells on the other side (right). Gray cells, losers; orange cells, winners. (B) Local interactions between cells identify relative metabolic status, triggering apoptosis in losers. Signals from dying cells (arrowheads) may stimulate the growth of winner cells. Cells to the right of the compartment boundary are completely protected. (C) Loser cells can be engulfed by winner cells. This process promotes winner-cell proliferation. (D) Winner cells expand their territory at the expense of loser cells. However, this expansion is limited to one compartment, because cells in the opposite compartment (right of the dotted line) remain insulated. The geographic limits of competition help stabilize organ size.

Fig. 3

Stem cells compete for their niche. (A) Depiction of the germarium (adapted from 26). (B) GSC competition. GSCs (blue and yellow) adhere to cap cells (green) in the niche via strong E-cadherin interactions. bam-mutant GSCs (blue) cannot differentiate, and they retain strong adherens junction (AJ) connections that can displace wild-type GSCs from the niche. (C) FSC competition. FSCs occupy a niche composed of the lateral edge of a 2a cyst encased in an escort cell (EC), the basement membrane (magenta line), and the FSC (red). Green circles are ring canal bridges. Arrows show direction of movement of the newly born FSC. The FSC can move posteriorly (bottom arrow) or toward the opposite niche (top arrows), where it can displace the resident FSC.