Deconvoluting the hematopoietic niche under stress

 描述(申请人提供)：在创伤、手术、败血症、镰状细胞危象和干细胞移植后的急性环境中，血细胞的产生对生存至关重要，但在这些环境中通常是功能失调的。我们最近使用了一种基于邻近性的单细胞分析来确定骨髓中独特的间充质细胞亚群，该亚群差异表达控制造血干和祖细胞静止的分子。这些分子，IL-18和血管生成素，在应激状态下受到不同的调节，我们假设，它们参与了功能失调的造血。我们试图确定这些特定分子在脓毒症和移植模型中的作用，以确定调节它们是否会改善血细胞的产生和存活。此外，我们寻求更广泛地扩展定义特定的骨髓基质细胞亚群的优势，并提出无偏见的单细胞分析工具来定义骨髓基质的复杂性以及它在应激环境中可能如何改变。

 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.