The establishment and maintenance of different cellular compartments in tissues is a universal requirement across multicellular organisms. Maintaining the correct ratio of cell types in time and space allows tissues to form patterned compartments and perform complex functions. Patterning is especially evident in the human colon, where tissue homeostasis is maintained by stem cells in crypt structures that balance proliferation and differentiation. We developed a system where human derived colon cells self-organize into regularly spaced proliferative regions separated by non-proliferative zones. Using this system, we discovered that waves of ERK signaling induced by apoptotic cells play a critical role in maintaining tissue patterning and homeostasis.