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. 2019 Jun 13;177(7):1915-1932.e16.
doi: 10.1016/j.cell.2019.04.040. Epub 2019 May 23.

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

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Free PMC article

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

Ninib Baryawno et al. Cell. .
Free PMC article

Abstract

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 sequencing (scRNA-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 including distinct osteoblast differentiation trajectories. Emerging acute myeloid leukemia impaired mesenchymal osteogenic differentiation and reduced regulatory molecules necessary for normal hematopoiesis. These data suggest that tissue stroma responds to malignant cells by disadvantaging normal parenchymal cells. Our taxonomy of the stromal compartment provides a comprehensive bone marrow cell census and experimental support for cancer cell crosstalk with specific stromal elements to impair normal tissue function and thereby enable emergent cancer.

Keywords: bone marrow niche; hematopoiesis; leukemia; single-cell RNA-sequencing; stem cell; stroma; tumor microenvironment.

Conflict of interest statement

Declaration of Interests

D.T.S., director and shareholder of Magenta Therapeutics, Agios Pharmaceuticals, Editas Medicines, Clear Creek Bio, Red Oak Medicines and LifeVaultBio; a shareholder of Fate Therapeutics, a consultant for Magenta Therapeutics, Clear Creek Bio, Red Oak Medicines, VCanBio and a SAB member of FOG Pharma. A.R., a founder and equity holder of Celsius Therapeutics; a member of the SAB for ThermoFisher Scientific and Syros Pharmaceuticals. M.S.K., employed by Celsius Therapeutics. The authors have filed for patent (62/808,177).

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