p53 drives a transcriptional program that elicits a non-cell-autonomous response and alters cell state in vivo
Sydney M. Moyer, Amanda R. Wasylishen, Yuan Qi, Natalie W. Fowlkes, Xiaoping Su, Guillermina Lozano
Abstract
Global p53 activation caused a metaplastic phenotype in the pancreas that was missing in mice with acinar-specific p53 activation, suggesting non-cell-autonomous effects. The p53 cellular response at single-cell resolution in the intestine altered transcriptional cell state, leading to a proximal enterocyte population enriched for genes within oxidative phosphorylation pathways. In addition, a population of active CD8+ T cells was recruited. Combined, this study provides a comprehensive profile of the p53 transcriptional response in vivo, revealing both tissue-specific transcriptomes and a unique signature, which were integrated to induce both cell-autonomous and non-cell-autonomous responses and transcriptional plasticity.