Back to Search
Start Over
The bone marrow microenvironment at single-cell resolution
The bone marrow microenvironment at single-cell resolution
- Source :
- Nature
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- The molecular complexity of the bone marrow (BM) microenvironment and its response to stress are incompletely understood, despite its key role in the regulation of hematopoiesis. Here we map the transcriptional landscape of BM vascular, perivascular, and osteoblast niche populations at single-cell resolution at both homeostasis and under stress hematopoiesis. This analysis revealed a previously unappreciated level of cellular heterogeneity within the BM niche, identified novel cellular subsets, and resolved cellular sources of pro-hematopoietic growth factors, chemokines, and membrane-bound ligands. Under conditions of stress, our studies revealed a significant transcriptional remodeling of these niche elements, including an adipocytic skewing of the perivascular cells. Among the stress-induced changes, we observed that vascular Notch ligand delta-like ligands (Dll1,4) were downregulated. In the absence of vascular Dll4, hematopoietic stem cells (HSC) prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the BM niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress, and illustrate the utility of single cell transcriptomic data in systematically evaluating the regulation of hematopoiesis by discrete niche populations.
- Subjects :
- Male
0301 basic medicine
Myeloid
Cellular differentiation
Biology
Article
Transcriptome
Mice
03 medical and health sciences
0302 clinical medicine
Single-cell analysis
Bone Marrow
Stress, Physiological
Adipocytes
medicine
Animals
Cell Lineage
Myeloid Cells
RNA-Seq
Stem Cell Niche
Adaptor Proteins, Signal Transducing
Regulation of gene expression
Osteoblasts
Multidisciplinary
Receptors, Notch
Calcium-Binding Proteins
Cell Differentiation
Hematopoietic Stem Cells
Hematopoiesis
Cell biology
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Cellular Microenvironment
Gene Expression Regulation
030220 oncology & carcinogenesis
Female
Endothelium, Vascular
Bone marrow
Single-Cell Analysis
Stem cell
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 569
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....dd188ba243ed1779b2b761ac1b0f86e2
- Full Text :
- https://doi.org/10.1038/s41586-019-1104-8