The cycling and aging mouse female reproductive tract at single-cell resolution

The female reproductive tract (FRT) undergoes extensive remodeling during reproductive cycling. This recurrent remodeling and how it shapes organ-specific aging remains poorly explored. Using single-cell and spatial transcriptomics, we systematically characterized morphological and gene expression changes occurring in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrous cycle, during decidualization, and into aging. These analyses reveal that fibroblasts play central-and highly organ-specific-roles in FRT remodeling by orchestrating extracellular matrix (ECM) reorganization and inflammation. Our results suggest a model wherein recurrent FRT remodeling over reproductive lifespan drives the gradual, age-related development of fibrosis and chronic inflammation. This hypothesis was directly tested using chemical ablation of cycling, which reduced fibrotic accumulation during aging. Our atlas provides extensive detail into how estrus, pregnancy, and aging shape the organs of the female reproductive tract and reveals the unexpected cost of the recurrent remodeling required for reproduction

Fruit Distribution in the Canadian West

Transcription factors, by binding to particular DNA sequences termed transcription factor-binding sites, play an important role in regulating gene expression in both prokaryotic and eukaryotic organisms. These binding sites lie within promoters (which are located just upstream of a gene and promote transcription of that gene) and enhancers (short DNA elements enhancing transcription levels of genes in a gene cluster, and which need not be particularly close to the genes they act on, or even located on the same chromosome). Binding of transcription factors in these genomic regulatory regions can influence gene transcription rates either positively or negatively. The binding may also be dependant on the interaction with co-activators and co-repressors, in addition to context (e.g. particular histone modifications in the vicinity of the regulatory element). Identifying all transcription factors and their respective binding sites would be an important step towards a more thorough understanding of gene regulation. Regular expression type patterns, as well as nucleotide distribution matrices, have both been used for describing transcription factor-binding sites, e.g. (Bucher 1990; Ghosh 1990; Chen et al. 1995; Wingender et al. 1996). Here we will discuss some of the computational approaches that are used in binding site identification.SCOPUS: ch.binfo:eu-repo/semantics/publishe

Sequence analysis of chromatin immunoprecipitation data for factors

Chromatin immunoprecipitation (ChIP) experiments allow the location of transcription factors to be determined across the genome. Subsequent analysis of the sequences of the identified regions allows binding to be localized at a higher resolution than can be achieved by current high-throughput experiments without sequence analysis and may provide important insight into the regulatory programs enacted by the protein of interest. In this chapter we review the tools, workflow, and common pitfalls of such analyses and recommend strategies for effective motif discovery from these data