Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency.

In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.

Missed training, collateral damage from COVID 19?

BACKGROUND: during the COVID-19 pandemic a total lockdown was enforced all over Italy starting on March 9th. This resulted in the shrinking of economic activities. In addition, all formal occupational security-training courses were halted, among them the 81/08 law lectures and Basic Life Support-Defibrillation (BLS-D) laymen training courses. The aim of the study was to evaluate the impact of the pandemic on BLS-D laymen training courses in the Lombardy region. METHODS: BLS-D training courses records for the Lombardy region were analysed. The analysis was conducted from 2016 to 2020 as part of the Hippo project. RESULTS: between 2017 and 2019 BLS-D trained laymen kept increasing, moving from 53,500 trained individuals up to 74,700. In 2020 a stark reduction was observed with only 22,160 individuals trained. Formal courses were not halted completely during 2020. Still, in the months available for training, the number of individuals enrolled showed a sharp 50% reduction. CONCLUSIONS: laymen training courses for emergency management are a fundamental component of primary prevention practice. The 81/08 and 158/12 Italian laws have decreed this practice mandatory on the workplace. Following the enforcement of the lockdown and the subsequent interruption of emergency management courses, efforts will be necessary to re-establish and guarantee the high quality training of the pre-pandemic period.