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Roberson, E. C.

Publications and source records attributed to Roberson, E. C..

4 recordsLinked to original sources

Gli3 is required for glandular epithelial proliferation and endometrial homeostasis during the estrous cycle

The endometrium is the innermost compartment of the uterus and undergoes cyclical remodeling throughout the human menstrual cycle and the rodent estrous cycle. The endometrium must thicken appropriately for embryonic implantation to occur; thus, it is crucial to understand the molecular mechanisms downstream of steroid hormone action that regulate endometrial thickness. Hedgehog (Hh) signaling is required for endometrial remodeling in both mice and humans, but the role of downstream Hh transcriptional effectors in endometrial remodeling is unknown. Here, we discover a role for the Hh transcriptional repressor, Gli3, in endometrial homeostasis: conditional knockout of Gli3 resulted in a constitutively thick endometrium throughout the estrous cycle. In our model, a constitutively thick endometrium could support pregnancy. Bulk RNA-sequencing data revealed that loss of Gli3 also resulted in dysregulated stromal-epithelial crosstalk, while immunofluorescent staining showed larger uterine glands and increased gland proliferation. These data deepen our understanding of molecular mechanisms controlling endometrial thickness, offering novel pathways to investigate endometrial factors in infertility.

cell biology↗

Single cell-scale spatial transcriptome profiling of the adult cycling mouse uterus

The adult uterus is highly regenerative during the reproductive cycle (menstrual in humans; estrous in mice), while the uterus prepares for a possible pregnancy. Until recently, the regenerative capacity of the mouse uterus was under-appreciated. Therefore, how uterine cell types and tissue compartments coordinate transcriptional and cellular changes across the estrous cycle is poorly understood. To begin to uncover the spatiotemporal molecular regulation of cell remodeling and regeneration, we conducted Visium HD spatial transcriptomics to analyze the adult cycling nulliparous mouse uterus. We integrated transcriptional data binned into 8x8 {micro}m spots across all four cycle stages to annotate cell types. This dataset provides highly resolved transcriptional information of uterine cell types, including luminal epithelium, glandular epithelium, mesenchyme, blood vessels, immune cells, and smooth muscle. These data can be used to define subpopulations of uterine cells and how they change in the adult cycling uterus or determine where disease-related genes are spatially expressed. Collectively, rigorous analysis of this dataset will significantly advance our understanding of uterine biology.

genomics↗

Iterative remodeling of the mouse uterus requires Hedgehog signaling

The adult uterus regenerates in the human during the menstrual cycle, and remodels in the mouse during the estrous cycle. Decades of work has demonstrated that this process is controlled by cycling steroid hormones, estrogen and progesterone. However, downstream signaling pathways that link hormonal action to this regeneration and remodeling are yet to be identified in the cycling uterus. We set out to identify these pathways, with the overarching hypothesis that developmental signaling pathways are redeployed in the adult uterus to control remodeling in the mouse. We were surprised to find that the majority of Hedgehog signaling components were transcriptionally co-regulated throughout the estrous cycle. To test the role of Hh signaling in cyclical uterine remodeling, we conditionally knocked out the major activator of the pathway, smoothened (Smo) using the progesterone receptor cre (PR-Cre). In the absence of Hh signaling, the uterus no longer remodels throughout the estrous cycle. We also show that the smooth muscle fibers of the uterus are significantly larger in the conditional knockouts compared to the controls suggesting hypertrophy of the smooth muscle. Our findings support the possibility that this smooth muscle homeostasis may underlie important aspects of uterine function such as contractility during late-stage pregnancy or the development of uterine smooth muscle tumors.

developmental biology↗

A Comparative Study of the Turnover of Multiciliated Cells in the Mouse Trachea, Oviduct and Brain

In mammals, multiciliated cells (MCCs) line the lumen of the trachea, oviduct, and brain ventricles, where they drive fluid flow across the epithelium. Each MCC population experiences vastly different local environments that may dictate differences in their lifetime and turnover rates. However, with the exception of MCCs in the trachea, the turnover rates of these multiciliated epithelial populations at extended time scales are not well described. Here, using genetic lineage-labeling techniques we provide a direct comparison of turnover rates of MCCs in these three different tissues. We find that oviduct turnover is similar to that in the airway ([~]6 months), while multiciliated ependymal cells turnover more slowly.

developmental biology↗