https://www.selleckchem.com/products/ly3537982.html All vaccines rely on the ability of B cells to remember pathogen infections and respond more vigorously upon reinfection. In this issue of Cell, Viant et al. address the real-world issue of protection against rapidly emerging pathogen variants and describe how memory B cells may anticipate infections by such variants.Whittington et al. demonstrate how network architectures defined in a spatial context may be useful for inference on different types of relational knowledge. These architectures allow for learning the structure of the environment and then transferring that knowledge to allow prediction of novel transitions.Lifelong blood production requires long-term hematopoietic stem cells (LT-HSCs), marked by stemness states involving quiescence and self-renewal, to transition into activated short-term HSCs (ST-HSCs) with reduced stemness. As few transcriptional changes underlie this transition, we used single-cell and bulk assay for transposase-accessible chromatin sequencing (ATAC-seq) on human HSCs and hematopoietic stem and progenitor cell (HSPC) subsets to uncover chromatin accessibility signatures, one including LT-HSCs (LT/HSPC signature) and another excluding LT-HSCs (activated HSPC [Act/HSPC] signature). These signatures inversely correlated during early hematopoietic commitment and differentiation. The Act/HSPC signature contains CCCTC-binding factor (CTCF) binding sites mediating 351 chromatin interactions engaged in ST-HSCs, but not LT-HSCs, enclosing multiple stemness pathway genes active in LT-HSCs and repressed in ST-HSCs. CTCF silencing derepressed stemness genes, restraining quiescent LT-HSCs from transitioning to activated ST-HSCs. Hence, 3D chromatin interactions centrally mediated by CTCF endow a gatekeeper function that governs the earliest fate transitions HSCs make by coordinating disparate stemness pathways linked to quiescence and self-renewal.Telomeres, repetitive terminal features of chrom