Browsing by Author "Hoggatt, Amber F."

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    Bleeding the laboratory mouse: Not all methods are equal
    (Elsevier, 2016-02) Hoggatt, Jonathan; Hoggatt, Amber F.; Tate, Tiffany A.; Fortman, Jeffrey; Pelus, Louis M.; Microbiology and Immunology, School of Medicine
    The laboratory mouse is the model most frequently used in hematologic studies and assessment of blood parameters across a broad range of disciplines. Often, analysis of blood occurs in a nonterminal manner. However, the small body size of the mouse limits collection based on volume, frequency, and accessible sites. Commonly used sites in the mouse include the retro-orbital sinus, facial vein, tail vein, saphenous vein, and heart. The method of blood acquisition varies considerably across laboratories and is often not reported in detail. In this study, we report significant alterations in blood parameters, particularly of total white blood cells, specific populations of dendritic cells and myeloid-derived suppressor cells, and hematopoietic progenitor cells, as a result of site and manner of sampling. Intriguingly, warming of mice prior to tail bleeding was found to significantly alter blood values. Our findings suggest that the same method should be used across an entire study, that mice should be warmed prior to tail bleeds to make levels uniform, and that accurate description of bleeding methods in publications should be provided to allow for interpretation of comparative reports and inter- and intralaboratory experimental variability.
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    Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2
    (Springer Nature, 2013) Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.; Medicine, School of Medicine
    To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.