Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling

Previous studies have identified Notch as a key regulator of hematopoietic stem cell (HSC) development, but the underlying downstream mechanisms remain unknown. The Notch target Hes1 is widely expressed in the aortic endothelium and hematopoietic clusters, though Hes1-deficient mice show no overt hematopoietic abnormalities. We now demonstrate that Hes is required for the development of HSC in the mouse embryo, a function previously undetected as the result of functional compensation by de novo expression of Hes5 in the aorta/gonad/mesonephros (AGM) region of Hes1 mutants. Analysis of embryos deficient for Hes1 and Hes5 reveals an intact arterial program with overproduction of nonfunctional hematopoietic precursors and total absence of HSC activity. These alterations were associated with increased expression of the hematopoietic regulators Runx1, c-myb, and the previously identified Notch target Gata2. By analyzing the Gata2 locus, we have identified functional RBPJ-binding sites, which mutation results in loss of Gata2 reporter expression in transgenic embryos, and functional Hes-binding sites, which mutation leads to specific Gata2 up-regulation in the hematopoietic precursors. Together, our findings show that Notch activation in the AGM triggers Gata2 and Hes1 transcription, and next HES-1 protein represses Gata2, creating an incoherent feed-forward loop required to restrict Gata2 expression in the emerging HSCs

A research data management (RDM) community for ELIXIR

Research data management (RDM) is central to the implementation of the FAIR (Findable Accessible, Interoperable, Reusable) and Open Science principles. Recognising the importance of RDM, ELIXIR Platforms and Nodes have invested in RDM and launched various projects and initiatives to ensure good data management practices for scientific excellence. These projects have resulted in a rich set of tools and resources highly valuable for FAIR data management. However, these resources remain scattered across projects and ELIXIR structures, making their dissemination and application challenging. Therefore, it becomes imminent to coordinate these efforts for sustainable and harmonised RDM practices with dedicated forums for RDM professionals to exchange knowledge and share resources.The proposed ELIXIR RDM Community will bring together RDM experts to develop ELIXIR’s vision and coordinate its activities, taking advantage of the available assets. It aims to coordinate RDM best practices and illustrate how to use the existing ELIXIR RDM services. The Community will be built around three integral pillars, namely, a network of RDM professionals, RDM knowledge management and RDM training expertise and resources. It will also engage with external stakeholders to leverage benefits and provide a forum to RDM professionals for regular knowledge exchange, capacity building and development of harmonised RDM practices, keeping in line with the overall scope of the RDM Community.In the short term, the Community aims to build upon the existing resources and ensure that the content of these remain up to date and fit for purpose. In the long run, the Community will aim to strengthen the skills and knowledge of its RDM professionals to support the emerging needs of the scientific community. The Community will also devise an effective strategy to engage with other ELIXIR structures and international stakeholders to influence and align with developments and solutions in the RDM field