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| Status |
Public on Nov 02, 2022 |
| Title |
Inflammation of the Aged Bone Marrow Niche Drives Blood Aging |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hematopoietic aging is defined by a loss of regenerative capacity and skewed differentiation from hematopoietic stem cells (HSC) leading to dysfunctional blood production. Signals from the bone marrow (BM) microenvironment dynamically tailor hematopoiesis, but the effect of aging on the niche and the contribution of the aging niche to blood aging still remains unclear. Here, we show the development of an inflammatory milieu in the aged marrow cavity, which drives both niche and hematopoietic system remodeling. We find decreased numbers and functionality of osteogenic endosteal mesenchymal stromal cells (MSC), expansion of pro-inflammatory perisinusoidal MSCs, and deterioration of the central marrow sinusoidal endothelium, which together create a self-reinforcing inflamed BM milieu. Single cell molecular mapping of old niche cells further confirms disruption of cell identities and enrichment of inflammatory response genes. Inflammation, in turn, drives chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors, which promotes myeloid differentiation at the expense of lymphoid and erythroid commitment, and hinders hematopoietic regeneration. Remarkably, both defective hematopoietic regeneration, niche deterioration and HSC aging can be improved by blocking inflammatory IL-1 signaling. Our results indicate that targeting the pro-inflammatory niche milieu can be instrumental in restoring blood production during aging.
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| Overall design |
RNA sequencing of mesenchymal and endothelial populations isolated from both endosteum and central marrow of young and old mice
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| Contributor(s) |
Verovskaya EV, Mitchell CA, Calero-Nieto FJ, Hérault A, Dellorusso PV, Wang X, Zhang SY, Svendsen AF, Bakker S, Pietras EM, Ho TT, Göttgens B, Passegué E |
| Citation(s) |
36650381 |
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| Submission date |
Mar 10, 2021 |
| Last update date |
Feb 02, 2023 |
| Contact name |
Bertie Gottgens |
| Organization name |
University of Cambridge
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| Department |
Haematology
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| Street address |
Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (661)
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| This SubSeries is part of SuperSeries: |
| GSE169162 |
Stromal niche inflammation mediated by IL-1 signaling is a targetable driver of hematopoietic aging |
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| Relations |
| BioProject |
PRJNA713010 |
| SRA |
SRP310082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168613_HTSeq_cnt.txt.gz |
6.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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