Dynamic chromatin remodeling in cycling human endometrium at single-cell level
Pavle Vrljicak,
Emma S. Lucas,
Maria Tryfonos,
Joanne Muter,
Sascha Ott,
Jan J. Brosens
Affiliations
Pavle Vrljicak
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK; The Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry CV4 7AL, UK
Emma S. Lucas
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK
Maria Tryfonos
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK
Joanne Muter
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK; Tommy’s National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire NHS Trust, Coventry CV2 2DX, UK
Sascha Ott
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK; The Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry CV4 7AL, UK
Jan J. Brosens
Warwick Medical School, Division of Biomedical Sciences, University of Warwick, Coventry CV2 2DX, UK; Tommy’s National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire NHS Trust, Coventry CV2 2DX, UK; Corresponding author
Summary: Estrogen-dependent proliferation followed by progesterone-dependent differentiation of the endometrium culminates in a short implantation window. We performed single-cell assay for transposase-accessible chromatin with sequencing on endometrial samples obtained across the menstrual cycle to investigate the regulation of temporal gene networks that control embryo implantation. We identify uniquely accessible chromatin regions in all major cellular constituents of the endometrium, delineate temporal patterns of coordinated chromatin remodeling in epithelial and stromal cells, and gain mechanistic insights into the emergence of a receptive state through integrated analysis of enriched transcription factor (TF) binding sites in dynamic chromatin regions, chromatin immunoprecipitation sequencing analyses, and gene expression data. We demonstrate that the implantation window coincides with pervasive cooption of transposable elements (TEs) into the regulatory chromatin landscape of decidualizing cells and expression of TE-derived transcripts in a spatially defined manner. Our data constitute a comprehensive map of the chromatin changes that control TF activities in a cycling endometrium at cellular resolution.
