A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia

被引：662

作者：

Baryawno, Ninib ^{[1
,2
,3
,4
]}

Przybylski, Dariusz ^{[5
]}

Kowalczyk, Monika S. ^{[5
]}

Kfoury, Youmna ^{[1
,2
,3
]}

Severe, Nicolas ^{[1
,2
,3
]}

Gustafsson, Karin ^{[1
,2
,3
]}

Kokkaliaris, Konstantinos D. ^{[1
,2
,3
]}

Mercier, Francois ^{[1
,2
,3
]}

Tabaka, Marcin ^{[5
]}

Hofree, Matan ^{[5
]}

Dionne, Danielle ^{[5
]}

Papazian, Ani ^{[1
,2
,3
]}

Lee, Dongjun ^{[1
,2
,3
,6
]}

Ashenberg, Orr ^{[5
]}

Subramanian, Ayshwarya ^{[5
]}

Vaishnav, Eeshit Dhaval ^{[5
]}

Rozenblatt-Rosen, Orit ^{[5
]}

Regev, Aviv ^{[5
,7
]}

Scadden, David T. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[2] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Karolinska Inst, Childhood Canc Res Unit, Dep Childrens & Womens Hlth, S-17177 Stockholm, Sweden

[5] Broad Inst Harvard & MIT, Klarman Cell Observ, Cambridge, MA 02142 USA

[6] Pusan Natl Univ, Dept Convergence Med Sci, Sch Med, Yangsan 50612, South Korea

[7] MIT, Dept Biol, Koch Inst Integrat Canc Res, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02142 USA

来源：

CELL | 2019年 / 177卷 / 07期

基金：

瑞典研究理事会;

关键词：

HEMATOPOIETIC STEM-CELL; ACUTE MYELOID-LEUKEMIA; AUTOSOMAL SEX REVERSAL; ENDOTHELIAL-CELLS; FUNCTIONAL INHIBITION; CAMPOMELIC DYSPLASIA; OSTEOBLASTIC CELLS; GENE-EXPRESSION; SELF-RENEWAL; IN-VIVO;

D O I：

10.1016/j.cell.2019.04.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1915 / +

页数：34

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