Project description:Methanotrophs, which help regulate atmospheric levels of methane, are active in diverse natural and man-made environments. This range of habitats and the feast-famine cycles seen by many environmental methanotrophs suggest that methanotrophs dynamically mediate rates of methane oxidation. Global methane budgets require ways to account for this variability in time and space. Functional gene biomarker transcripts are increasingly being studied to inform the dynamics of diverse biogeochemical cycles. Previously, per-cell transcript levels of the methane oxidation biomarker, pmoA, were found to vary quantitatively with respect to methane oxidation rates in model aerobic methanotroph, Methylosinus trichosporium OB3b. In the present study, these trends were explored for two additional aerobic methanotroph pure cultures, Methylocystis parvus OBBP and Methylomicrobium album BG8. At steady-state conditions, per cell pmoA mRNA transcript levels strongly correlated with per cell methane oxidation across the three methanotrophs across many orders of magnitude of activity (R2 = 0.91). Additionally, genome-wide expression data (RNA-seq) were used to explore transcriptomic responses of steady state M. album BG8 cultures to short-term CH4 and O2 limitation. These limitations induced regulation of genes involved in central carbon metabolism (including carbon storage), cell motility, and stress response.
Project description:NANOG is a key transcription factor for pluripotency in embryonic stem cells. However, its role in adult tissues remains largely unexplored. Here, we show that mouse NANOG is expressed in the progenitor layer of stratified epithelia, including esophagus, forestomach and skin. Accordingly, the Nanog promoter is hypomethylated in the epithelial layers of the esophagus and forestomach. Interestingly, ubiquitous transgenic overexpression of NANOG in mice induces hyperplasia in stratified epithelia, but not in other tissues. Mechanistically, we show that NANOG transcriptionally activates the mitotic program selectively in stratified epithelia, and endogenous NANOG directly binds the Aurora kinase A (Aurka) promoter in keratinocytes. Finally, human and mouse squamous cell carcinomas (SCCs) express NANOG and its levels positively correlate with those of AURKA in human head and neck SCCs. Together, these results implicate a lineage-restricted mitogenic role of NANOG in normal stratified epithelia and its derived carcinomas.
Project description:Our findings indicate that the integration of expression signatures and clinicopathological factors can better determine the individual risk of recurrence for newly diagnosed patients with lymph-node negative ER-positive breast cancer. Models incorporating other variables yet to be discovered will be needed to obtain robust prognostic models for ER-negative and HER2-positive breast cancer patients.