Inhomogeneous mechanotransduction defines the spatial pattern of apoptosis-induced compensatory proliferation

Abstract

The number of cells in tissues is controlled by cell division and cell death, and its misregulation could lead to pathological conditions such as cancer. To maintain the cell numbers, a cell-elimination process called apoptosis also stimulates the proliferation of neighboring cells. This mechanism, apoptosis-induced compensatory proliferation, was originally described more than 40 years ago. Although only a limited number of the neighboring cells need to divide to compensate for the apoptotic cell loss, the mechanisms that select cells to divide have remained elusive. Here, we found that spatial inhomogeneity in Yes-associated protein (YAP)-mediated mechanotransduction in neighboring tissues determines the inhomogeneity of compensatory proliferation in Madin-Darby canine kidney (MDCK) cells. Such inhomogeneity arises from the non-uniform distribution of nuclear size and the non-uniform pattern of mechanical force applied to neighboring cells. Our findings from a mechanical perspective provide additional insight into how tissues precisely maintain homeostasis.

Keywords: YAP; apoptosis; cell division; compensatory proliferation; mechanotransduction; tissue homeostasis.