DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2–5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cellfree virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions.IMPORTANCE In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fe-

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To compare anatomic and clinical cure rates as well as patient satisfaction between uterine-preserving laparoscopic uterosacral ligament suspension and total vaginal hysterectomy with uterosacral ligament suspension in women with apical and anterior prolapse. Design: Single-center clinical comparative retrospective cohort study. Setting: A female pelvic medicine and reconstructive surgery service at a tertiary teaching hospital. Patients: Women with pelvic organ prolapse who underwent surgical treatment for their condition between July 2010 and December 2015. Interventions: All women underwent laparoscopic uterosacral ligament suspension or total vaginal hysterectomy with uterosacral ligament suspension for apical and anterior prolapse. Concomitant procedures included anterior and posterior repair, as well as a midurethral sling when indicated. Measurements and Main Results: Preoperative and postoperative Pelvic Organ Prolapse Quantification (POP-Q) measurements were obtained. The primary outcome was clinical cure rate. Secondary outcomes included anatomic cure rate and outcomes of site-specific POP-Q points Ba, C, and Bp for the whole cohort. Patient satisfaction was measured using the Patient Global Impression of Improvement questionnaire. During the study period, 106 women underwent transvaginal hysterectomy with uterosacral ligament suspension, and 53 women had laparoscopic uterosacral ligament suspension. At a mean follow-up of 14.7 § 13.23 months for the vaginal group and 17.5 § 15.84 months for the laparoscopic group (p = .29), there were significant improvements of POP-Q points Ba, C, and Bp (p < .0001 for all comparisons in both groups). The clinical cure rate was 96% in the vaginal group and 98% in the laparoscopic group (p = .50). The anatomic cure rate was 85.4% in the vaginal group and 93.75% in the laparoscopic group (p = .11) Patient satisfaction was high in both groups. Conclusion: In appropriately selected patients, laparoscopic uterosacral ligament suspension is a valid uterus-preserving option for women with anterior and apical prolapse, associated with high anatomic and clinical cure rates and patient satisfaction.