The bone marrow microenvironment at single-cell resolution
| Autor: | Edlira Hoxha, Catherine Diefenbach, Yutong Zhang, Adriana Heguy, Anastasia N. Tikhonova, Stavroula Kousteni, Kishor K. Sivaraj, Aristotelis Tsirigos, Hai Hu, Ralf H. Adams, Igor Dolgalev, Aris N. Economides, Matthew T. Witkowski, Ilseyar Akhmetzyanova, Michael C. Gutkin, Jason M. Butler, Maria Guillamot, Álvaro Cuesta-Domínguez, Jie Gao, Sandra Pinho, Hua Zhong, Paul S. Frenette, Rahul Satija, David R. Fooksman, Christian Marier, Iannis Aifantis |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/s41586-019-1104-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink