A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia
A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia
复制标题
DOI：
10.1016/j.cell.2019.04.040
复制
发表时间：
2019-06-13
期刊：
影响因子：
64.5
通讯作者：
Scadden, David T.
中科院分区：
文献类型：
--
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
间质是几乎每个器官的一种模糊的非实质成分，在器官发育、动态平衡和修复中起着关键作用。对骨髓基质的研究已经确定了干细胞利基中的个体群体，这些群体调节着造血再生，并能够引发白血病。在这里，我们使用单细胞RNA-seq来定义小鼠骨髓基质的细胞分类学及其受恶性肿瘤的干扰。我们确定了17个基质亚群，表达不同的造血调控基因，跨越新的成纤维细胞和成骨细胞亚群。新出现的急性髓系白血病导致成骨分化受损，正常造血所需的造血调控分子的产生减少。因此，癌症可以影响它们所在的组织间质，从而使正常的实质细胞处于不利地位。我们对调节间质间隔的分类为一个模型提供了实验支持，在该模型中，恶性克隆不是正常组织的破坏者，而是它的建筑师，重塑组织间质，使癌症发生。
Stroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA-seq to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes, spanning new fibroblastic, and osteoblastic subpopulations. Emerging acute myeloid leukemia resulted in impaired osteogenic differentiation and reduced production of hematopoietic regulatory molecules necessary for normal hematopoiesis. Thus, cancer can affect tissue stroma in which they reside to disadvantage normal parenchymal cells. Our taxonomy of the regulatory stromal compartment provides experimental support for a model where malignant clone is not a destroyer of normal tissue but an architect of it, remodeling tissue stroma to enable emergent cancer.