Search

The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of the differentiation dynamics of the ExE and its interactions with the embryo proper remains incomplete. Here we develop a temporal single-cell model of mouse gastrulation that maps continuous and parallel differentiation in embryonic and extraembryonic lineages. This is matched with a three-way perturbation approach to target signalling from the embryo proper, the ExE alone, or both. We show that ExE specification involves early spatial and transcriptional bifurcation of uncommitted ectoplacental cone cells and chorion progenitors. Early BMP4 signalling from chorion progenitors is required for proper differentiation of uncommitted ectoplacental cone cells and later for their specification towards trophoblast giant cells. We also find biphasic regulation by BMP4 in the embryo. The early ExE-originating BMP4 signal is necessary for proper mesoendoderm bifurcation and for allantois and primordial germ cell specification. However, commencing at embryonic day 7.5, embryo-derived BMP4 restricts the primordial germ cell pool size by favouring differentiation of their extraembryonic mesoderm precursors towards an allantois fate. ExE and embryonic tissues are therefore entangled in time, space and signalling axes, highlighting the importance of their integrated understanding and modelling in vivo and in vitro., (© 2024. The Author(s).)

Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure., Competing Interests: Declaration of interests M.Z.-G. is an advisory board member of Cell Stem Cell. M.Z.-G. and G.A. wish to declare the filing of a patent on May 5(th), 2022 by Caltech and the University of Cambridge on the “Generation of synthetic embryos from multiple stem cell types.” The patent was filed under the following numbers: CIT File No.: CIT-8826-P and Serial Number: 63/344,251., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mice deficient for all ten-eleven translocation (TET) genes exhibit early gastrulation lethality. However, separating cause and effect in such embryonic failure is challenging. To isolate cell-autonomous effects of TET loss, we used temporal single-cell atlases from embryos with partial or complete mutant contributions. Strikingly, when developing within a wild-type embryo, Tet-mutant cells retain near-complete differentiation potential, whereas embryos solely comprising mutant cells are defective in epiblast to ectoderm transition with degenerated mesoderm potential. We map de-repressions of early epiblast factors (e.g., Dppa4 and Gdf3) and failure to activate multiple signaling from nascent mesoderm (Lefty, FGF, and Notch) as likely cell-intrinsic drivers of TET loss phenotypes. We further suggest loss of enhancer demethylation as the underlying mechanism. Collectively, our work demonstrates an unbiased approach for defining intrinsic and extrinsic embryonic gene function based on temporal differentiation atlases and disentangles the intracellular effects of the demethylation machinery from its broader tissue-level ramifications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether participating in childbirth classes is associated with pregnancy outcomes., Methods: A retrospective study was conducted to review the medical records of all nulliparous women who participated in childbirth classes during their pregnancy and delivered in the authors' institute, between January 2014 and December 2017 (CB class group). The control group comprised nulliparous women who delivered in the same time period, but who did not participate in any education classes (Not attended CB class group). The controls were matched in a ratio of 1:1 for gestational age at delivery and neonatal birth weight., Results: Overall, 159 patients were included in each group. The class group was characterized with above average income (28 [23.9%] vs 19 [16.7%]; P=0.001) and higher education level (80 [64.0%] vs 60 [45.1%]; P=0.002), higher rate of normal vaginal delivery (128 [80.5%] vs 93 [58.5%]; P<0.001), and lower rate of vacuum extraction (12 [7.5%] vs 36 [22.6%]; P<0.001) compared to the Not attended CB class group. By logistic regression analysis, after controlling for obstetrics and socioeconomic variables, participation in childbirth classes was found to be independently associated with successful normal vaginal delivery (odds ratio 2.90; 95% confidence interval 1.13-7.38; P=0.024)., Conclusion: Participation in childbirth classes has a positive impact on pregnancy outcome., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Healthcare workers (HCWs) are encouraged to get vaccinated during influenza pandemics to reduce their own, and patients', risk of infection, and to encourage their patients to get immunised. Despite extensive research on HCWs' receipt of vaccination, little is known about how HCWs articulate pandemic influenza vaccination advice to patients., Aims: To explore HCWs' uptake of the A/H1N1 vaccine during the pandemic of 2009-2010, their recommendations to patients at the time, and their anticipated choices around influenza vaccination under different pandemic scenarios., Method: We conducted semi-structured interviews and focus groups with eight vaccinated and seventeen non-vaccinated HCWs from primary care practices in England. The data was analysed using thematic analysis., Results: The HCWs constructed their receipt of vaccination as a personal choice informed by personal health history and perceptions of vaccine safety, while they viewed patients' vaccination as choices made following informed consent and medical guidelines. Some HCWs received the A/H1N1 vaccine under the influence of their local practice organizational norms and values. While non-vaccinated HCWs regarded patients' vaccination as patients' choice, some vaccinated HCWs saw it also as a public health issue. The non-vaccinated HCWs emphasised that they would not allow their personal choices to influence the advice they gave to patients, whereas some vaccinated HCWs believed that by getting vaccinated themselves they could provide a reassuring example to patients, particularly those who have concerns about influenza vaccination. All HCWs indicated they would accept vaccination under the severe pandemic scenario. However, most non-vaccinated HCWs expressed reticence to vaccinate under the mild pandemic scenario., Conclusions: Providing evidence-based arguments about the safety of new vaccines and the priority of public health over personal choice, and creating strong social norms for influenza vaccination as part of the organizational culture, should increase uptake of influenza vaccination among primary care HCWs and their patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)