Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. 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 new 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.
","abstract_html":"<p>Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood <em>in vivo</em>. We activated a p53 transcriptional program in mice by deletion of <em>Mdm2</em>, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included <em>Mdm2</em> but not <em>p21</em>. 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 new 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 <em>in vivo</em>, 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.</p>","abstract_has_math":false,"creators":["Moyer, Sydney","0000-0002-2911-4058
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"]},{"key":"dc:title","label":"Title","values":["P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response and Alters Cell State In Vivo"]}]}],"canonical_facts":{"dc:contributor":["Guillermina Lozano, Ph.D.","Michelle C. Barton, Ph.D.","Vicki Huff, Ph.D."],"dc:creator":["Moyer, Sydney","0000-0002-2911-4058
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"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1048"],"dc:subject":["p53","transcription","Mdm2","single cell RNA-sequencing","transcription factor","tissue-specific","non-cell-autonomous","genetics","Cancer Biology","Cell Biology","Genomics","Medicine and Health Sciences","Molecular Biology","Molecular Genetics"],"dc:title":["P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response and Alters Cell State In Vivo"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:41Z"}