Elucidating the mechanisms underlying hematopoietic stem cell (HSC) specification and expansion in the embryo has been hampered by the lack of analytical cell culture systems that recapitulate in vivo development. Here, we describe an ex vivo model that facilitates a rapid and robust emergence of multipotent long-term repopulating HSCs in the embryonic AGM region. Because this method includes a cell dissociation step prior to reconstruction of a three-dimensional functional tissue and preserves both stromal and hematopoietic elements, it allowed us to identify the direct ancestry of the rapidly expanding HSC pool. We demonstrate that extensive generation of definitive HSCs in the AGM occurs predominantly through the acquisition of stem characteristics by the VE-cadherin+CD45+ population.

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The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies have characterized the pathological changes that occur within adipose tissue in the obese state. One significant change is the dysregulation of adipokine production. Adipokines are an indispensable link between metabolism and optimal immune system function; however, their dysregulation in obesity contributes to chronic low-grade inflammation and disease pathology. Herein, I will highlight current knowledge on adipokine structure and physiological function, and focus on the known roles of these factors in the modulation of the immune response. I will also discuss adipokines in rheumatic and autoimmune diseases.

Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks – the oldest vertebrate group having adaptive immunity – also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate‐like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well‐defined, highly vascularized white pulp (WP) areas, composed of a central T‐cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B‐cell zones containing sIgM+–MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)‐expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult‐like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a ‘mature immune‐responsive environment’. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination‐activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.