Spatial transcriptomics analysis of uterine gene expression in enhancer of zeste homolog 2 conditional knockout mice†
| Autor: | Ana M Mesa, Theresa I. Medrano, Geetu Tuteja, Jiude Mao, Nathan J. Bivens, Paul S. Cooke, Alexander Jurkevich, Cheryl S. Rosenfeld |
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| Rok vydání: | 2021 |
| Předmět: |
Mice
Knockout Stromal cell Gene Expression Profiling Uterus EZH2 Cell Biology General Medicine Biology Chromatin Cell biology Mice medicine.anatomical_structure Reproductive Medicine Histone methyltransferase Gene expression Conditional gene knockout medicine Animals Enhancer of Zeste Homolog 2 Protein Female Epigenetics Uterine gland Transcriptome Research Article |
| Zdroj: | Biol Reprod |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1093/biolre/ioab147 |
| Popis: | Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. 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. |
| Databáze: | OpenAIRE |
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