TY - JOUR TI - Live-cell imaging in human colonic monolayers reveals ERK waves limit the stem cell compartment to maintain epithelial homeostasis AU - Pond, Kelvin W AU - Morris, Julia M AU - Alkhimenok, Olga AU - Varghese, Reeba P AU - Cabel, Carly R AU - Ellis, Nathan A AU - Chakrabarti, Jayati AU - Zavros, Yana AU - Merchant, Juanita L AU - Thorne, Curtis A AU - Paek, Andrew L A2 - Klein, Ophir D A2 - Stainier, Didier YR VL - 11 PY - 2022 DA - 2022/09/12 SP - e78837 C1 - eLife 2022;11:e78837 DO - 10.7554/eLife.78837 UR - https://doi.org/10.7554/eLife.78837 AB - The establishment and maintenance of different cellular compartments in tissues is a universal requirement across all metazoans. 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. Here, we developed a human 2D patient derived organoid screening platform to study tissue patterning and kinase pathway dynamics in single cells. Using this system, we discovered that waves of ERK signaling induced by apoptotic cells play a critical role in maintaining tissue patterning and homeostasis. If ERK is activated acutely across all cells instead of in wave-like patterns, then tissue patterning and stem cells are lost. Conversely, if ERK activity is inhibited, then stem cells become unrestricted and expand dramatically. This work demonstrates that the colonic epithelium requires coordinated ERK signaling dynamics to maintain patterning and tissue homeostasis. Our work reveals how ERK can antagonize stem cells while supporting cell replacement and the function of the gut. KW - colon KW - crypt KW - stem cells KW - epithelium KW - apoptosis KW - homeostasis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -