Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell Rep. 2021 May 11;35(6):109119. doi: 10.1016/j.celrep.2021.109119.
The bone-marrow (BM) niche is the spatial environment composed by a network of multiple stromal components regulating adult hematopoiesis. We use multi-omics and computational tools to analyze multiple BM environmental compartments and decipher their mutual interactions in the context of acute myeloid leukemia (AML) xenografts. Under homeostatic conditions, we find a considerable overlap between niche populations identified using current markers. Our analysis defines eight functional clusters of genes informing on the cellular identity and function of the different subpopulations and pointing at specific stromal interrelationships. We describe how these transcriptomic profiles change during human AML development and, by using a proximity-based molecular approach, we identify early disease onset deregulated genes in the mesenchymal compartment. Finally, we analyze the BM proteomic secretome in the presence of AML and integrate it with the transcriptome to predict signaling nodes involved in niche alteration in AML.
骨髓（BM）龛是由多个基质成分组成的空间环境，调节成人生成血。我们使用多组学和计算工具来分析多个 BM 环境隔室，并在急性髓系白血病（AML）异种移植物的背景下破译它们的相互作用。在稳态条件下，我们发现使用当前标记物识别的龛种群之间有相当大的重叠。我们的分析定义了八个功能基因簇，这些基因簇提供了不同亚群的细胞身份和功能信息，并指出了特定的基质相互关系。我们描述了这些转录组谱如何在人 AML 发展过程中发生变化，并通过使用基于邻近的分子方法，鉴定间充质隔室中早期疾病发病失调的基因。最后，我们分析了 AML 存在时的 BM 蛋白质组分泌组，并将其与转录组整合，以预测 AML 中龛改变涉及的信号节点。
