Deconvoluting the hematopoietic niche under stress

Massachusetts General Hospital, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): Blood cell production in the acute settings of trauma, surgery, sepsis, sickle cell crisis and after stem cell transplant is critical for survival and yet is often dysfunctional in those settings. We have recently used a single cell, proximity based analysis to define a distinctive mesenchymal cell subpopulation in the bone marrow that differentially expresses molecules governing hematopoietic stem and progenitor quiescence. These molecules, IL-18 and angiogenin are differentially regulated with stress and we hypothesize, participate in dysfunctional hematopoiesis. We seek to define the role of these specific molecules in models of sepsis and transplant to determine if modulating them will improve blood cell production and survival. Further, we seek to extend the advantage of defining specific subsets of marrow stromal cells more broadly and propose unbiased, single cell analytic tools to define the complexity of marrow stroma and how it may be altered in settings of stress.