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Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that methylates lysine residue 27, and thereby suppresses gene expression. EZH2 plays integral roles in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNA-seq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and\/or ablation of this gene would disrupt normal epithelial\/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.<\/jats:p>","DOI":"10.1093\/biolre\/ioab147","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T23:30:22Z","timestamp":1628033422000},"page":"1126-1139","source":"Crossref","is-referenced-by-count":15,"title":["Spatial transcriptomics analysis of uterine gene expression in enhancer of zeste homolog 2 conditional knockout mice\u2020"],"prefix":"10.1093","volume":"105","author":[{"given":"Ana M","family":"Mesa","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, Florida, USA"},{"name":"Grupo de Investigaci\u00f3n en Agrociencias, Biodiversidad y Territorio - GAMMA, Facultad de Ciencias Agrarias, Universidad de Antioquia UdeA, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiude","family":"Mao","sequence":"additional","affiliation":[{"name":"Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"},{"name":"Biomedical Sciences, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa I","family":"Medrano","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J","family":"Bivens","sequence":"additional","affiliation":[{"name":"Genomics Technology Core, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Jurkevich","sequence":"additional","affiliation":[{"name":"Advanced Light Microscopy Core Facility, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetu","family":"Tuteja","sequence":"additional","affiliation":[{"name":"Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl S","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, University of Missouri, Columbia, Missouri, USA"},{"name":"Data Science and Informatics Institute, University of Missouri, Columbia, Missouri, USA"},{"name":"Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"2021121822424369200_ref1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene 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