A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia
Name
nihms-1529101.pdf
Description
Accepted version
Size
4.02 MB
Format
Adobe PDF
Checksum (MD5)
9d998284a1bdb260aa3384456450e60c
Author(s)
Baryawno, Ninib
Przybylski, Dariusz
Kowalczyk, Monika S.
Kfoury, Youmna
Severe, Nicolas
Gustafsson, Karin
Kokkaliaris, Konstantinos D.
Mercier, Francois
Tabaka, Marcin
Hofree, Matan
Date Issued
June 2019
Journal
Cell
Publisher
Elsevier BV
Citation
Baryawno, Ninib et al. "A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia." Cell 177, 7 (June 2019): P1915-1932.e16 © 2019 Elsevier
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2019.04.040
