Graphical Abstract Highlights d Epigenome landscape maps reveal key transitions during epidermal lineage commitment d Network modeling identifies master regulators of lineage initiation and maturation d TFAP2C drives chromatin dynamics during initiation and primes p63-dependent maturation d Crosstalk between TFAP2C and p63 drives epigenetic transitions during differentiation

BackgroundThe impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. MethodsWe did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence,

Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine 1 – 3 , yet conversion into transplantable tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 4 , 5 during surface ectoderm commitment. In contrast to other master regulators 6 – 9 , p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 modifications. Cohesin HiChIP 10 visualizations of chromosome conformation reveal that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated with TFAP2C regulation 11 . Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by specific morphogen exposure.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes. Methods: This was a retrospective multicenter cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people that delivered (n=86,833) at Providence St. Joseph Health across Alaska, California, Montana, Oregon, New Mexico, Texas, and Washington from January 26, 2021 through July 11, 2022. Cohorts were defined by vaccination status at time of delivery: unvaccinated (n=48,492), unvaccinated propensity score matched (n=26,790), vaccinated (n=26,792; two doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), and/or boosted (n=7,616). The primary outcome was maternal COVID-19 infection. COVID-19 vaccination status at delivery, COVID-19 infection-related health care, preterm birth, stillbirth, very low birth weight, and small for gestational age were evaluated as secondary outcomes. Findings: Vaccinated pregnant people were significantly less likely to have a maternal COVID-19 infection than unvaccinated matched (p<0.0001) pregnant people. During a maternal COVID-19 infection, vaccinated pregnant people had similar rates of hospitalization (p=0.23), but lower rates of supplemental oxygen (p<0.05) or vasopressor (p<0.05) use than those in an unvaccinated matched cohort. Compared to an unvaccinated matched cohort, vaccinated people had significantly lower stillbirth rate (p<0.01) as well as no difference in rate of preterm birth (p=0.35), small for gestational age (p=0.79), or rate of very low birth weight (>1,500 g; 0.31). People who were vaccinated who had not received boosters had significantly lower rates of maternal COVID-19 infections (p<0.0001), COVID-19 related hospitalization (p<0.05), preterm birth (p<0.05), stillbirth (p<0.01), small for gestational age (p<0.05), and very low birth weight (p<0.01), compared to vaccinated people that did not receive a third booster shot five months after completing the initial vaccination series. Interpretation: COVID-19 vaccination protects against adverse maternal-fetal outcomes with booster shots conferring additional protection against COVID-19 infection. It is therefore important for pregnant people to have high priority status for vaccination, and for them to stay current with their COVID-19 vaccination schedule. Funding: This study was funded by the National Institute for Child Health & Human Development and the William O. and K. Carole Ellison Foundation.

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