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Nature. 2019 May;569(7755):222-228. doi: 10.1038/s41586-019-1104-8. Epub 2019 Apr 10.

The bone marrow microenvironment at single-cell resolution.

Author information

1
Department of Pathology, NYU School of Medicine, New York, NY, USA. Anastasia.Tikhonova@nyumc.org.
2
Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY, USA. Anastasia.Tikhonova@nyumc.org.
3
Department of Pathology, NYU School of Medicine, New York, NY, USA.
4
Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY, USA.
5
Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY, USA.
6
Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Münster, Germany.
7
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
8
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY, USA.
9
Department of Pathology, Albert Einstein College of Medicine, New York, NY, USA.
10
Regeneron Genetics Center, Tarrytown, NY, USA.
11
Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USA.
12
Genome Technology Center, Division of Advanced Research Technologies, NYU School of Medicine, New York, NY, USA.
13
Division of Biostatistics, Department of Population Health, NYU School of Medicine, New York, NY, USA.
14
New York Genome Center, New York, NY, USA.
15
Department of Pathology, NYU School of Medicine, New York, NY, USA. Aristotelis.Tsirigos@nyumc.org.
16
Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY, USA. Aristotelis.Tsirigos@nyumc.org.
17
Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY, USA. Aristotelis.Tsirigos@nyumc.org.
18
Department of Pathology, NYU School of Medicine, New York, NY, USA. Iannis.Aifantis@nyumc.org.
19
Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY, USA. Iannis.Aifantis@nyumc.org.

Abstract

The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single-cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands. Our studies demonstrate a considerable transcriptional remodelling of niche elements under stress conditions, including an adipocytic skewing of perivascular cells. Among the stress-induced changes, we observed that vascular Notch delta-like ligands (encoded by Dll1 and Dll4) were downregulated. In the absence of vascular Dll4, haematopoietic stem cells prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the bone marrow niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress and illustrate the utility of single-cell transcriptomic data in evaluating the regulation of haematopoiesis by discrete niche populations.

PMID:
30971824
DOI:
10.1038/s41586-019-1104-8

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