The yolk sac (YS) represents an evolutionarily-conserved extraembryonic structure that ensures timely delivery of nutritional support and oxygen to the developing embryo. However, the YS remains ill-defined in humans. We therefore assemble a complete single cell 3D map of human YS from 3-8 post conception weeks by integrating multiomic protein and gene expression data. We reveal the YS as a site of primitive and definitive haematopoiesis including a YS-specific accelerated route to macrophage production, a source of nutritional/metabolic support and a regulator of oxygen-carrying capacity. We reconstruct the emergence of primitive haematopoietic stem and progenitor cells from YS hemogenic endothelium and their decline upon stromal support modulation as intraembryonic organs specialise to assume these functions. The YS therefore functions as 'three organs in one' revealing a multifaceted relay of vital organismal functions as pregnancy proceeds. One Sentence Summary: Human yolk sac is a key staging post in a relay of vital organismal functions during human pregnancy.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the format itself -- OME-Zarr -- along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain -- the file format that underlies so many personal, institutional, and global data management and analysis tasks.

This is the first demonstration that bile acids induce TGF-β1 and MMP-9 in pharyngeal cells. TGF-β1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets.

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75Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic 76 stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single 77 cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify 78 the repertoire of blood and immune cells in first and early second trimesters of development. From this 79 data, we infer differentiation trajectories from HSC/MPPs, and evaluate the impact of tissue 80 microenvironment on blood and immune cell development. We predict coupling of mast cell 81 differentiation with erythro-megakaryopoiesis and identify physiological erythropoiesis in fetal skin. 82We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being 83 erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which 84 we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the 85 study of paediatric blood and immune disorders, and a valuable reference for understanding and 86 harnessing the therapeutic potential of HSC/MPPs. 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106