During early human pregnancy, the fetal placenta implants into the uterine mucosa (decidua)where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblastdecidual interactions underlie common diseases of pregnancy including pre-eclampsia and stillbirth. Here, we profile transcriptomes of ~70,000 single cells from first trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals new subsets of perivascular and stromal cells, which are located in distinct decidual layers.There are three major subsets of decidual NK cells, with distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes (https://cellphonedb.org/) and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. This identifies many regulatory interactions that prevent any damaging innate or adaptive immune responses in this environment. Our single cell atlas of the maternal-fetal interface reveals the cellular organization and interactions critical for placentation and reproductive success.During early pregnancy, the uterine mucosal lining, the endometrium, is transformed into decidua under the influence of progesterone. Decidualisation results from a complex and well-orchestrated differentiation program that involves all cellular elements of the mucosa: stromal, glandular, and immune cells, including the distinctive decidual Natural Killer cells (dNK) 1,2 . The blastocyst implants into the decidua and initially, before arterial connections are established, uterine glands are the source of histotrophic nutrition in the placenta 3,4 . Following implantation, placental extravillous trophoblast cells (EVT) invade through the decidua and move towards the spiral arteries, where they destroy the smooth muscle media and transform the arteries into high conductance vessels 5 . Balanced regulation of EVT invasion is critical to pregnancy success: arteries must be sufficiently transformed, but excessive invasion prevented, to ensure correct allocation of resources to both mother and baby 6 . The pivotal regulatory role of the decidua is obvious from the life-threatening, uncontrolled, trophoblast invasion that occurs when the decidua is absent as when the placenta implants on a previous cesarean section scar 7 .EVT have a unique HLA profile: they do not express the dominant T cell ligands, class I HLA-A and HLA-B or class II molecules 8,9 , but do express HLA-G and HLA-E and polymorphic HLA-C class I molecules. These trophoblast HLA ligands have receptors expressed by the dominant decidual immune cells, dNK, including maternal killer immunoglobulin-like receptors (KIR), that bind HLA-C molecules 10,11 . Certain combinations of maternal KIR and fetal HLA-C genetic variants are associated with pregnancy disorders such as pre-eclampsia, where trophoblast invasion is deficient 12 . However, detailed understanding of the cellular interactions in the decidua supporting early...

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

SummaryCTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution. To gain insight into how these DNA elements are conserved and spread through the genome, we defined the full spectrum of CTCF-binding sites, including a 33/34-mer motif, and identified over five thousand highly conserved, robust, and tissue-independent CTCF-binding locations by comparing ChIP-seq data from six mammals. Our data indicate that activation of retroelements has produced species-specific expansions of CTCF binding in rodents, dogs, and opossum, which often functionally serve as chromatin and transcriptional insulators. We discovered fossilized repeat elements flanking deeply conserved CTCF-binding regions, indicating that similar retrotransposon expansions occurred hundreds of millions of years ago. Repeat-driven dispersal of CTCF binding is a fundamental, ancient, and still highly active mechanism of genome evolution in mammalian lineages.PaperClip