Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
Abstract Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models.
- Heidelberg University Germany
- University of Geneva Switzerland
- University of Oxford United Kingdom
- European Molecular Biology Laboratory Germany
- Barcelona Institute for Science and Technology Spain
Adult, Male, Aging, Proteome, Science, Bone Marrow Cells, Article, Young Adult, Humans, Stem Cell Niche, Hematopoietic Stem Cells/cytology/metabolism, Aging/genetics/metabolism/pathology, Cellular Senescence, Bone Marrow Cells/cytology/metabolism, Gene Expression Profiling, Q, Adult Stem Cells/cytology, Middle Aged, Hematopoietic Stem Cells, Carbon, Hematopoiesis, Adult Stem Cells, Cellular Senescence/genetics, Carbon/metabolism, Female, ddc:570, Glycolysis
Adult, Male, Aging, Proteome, Science, Bone Marrow Cells, Article, Young Adult, Humans, Stem Cell Niche, Hematopoietic Stem Cells/cytology/metabolism, Aging/genetics/metabolism/pathology, Cellular Senescence, Bone Marrow Cells/cytology/metabolism, Gene Expression Profiling, Q, Adult Stem Cells/cytology, Middle Aged, Hematopoietic Stem Cells, Carbon, Hematopoiesis, Adult Stem Cells, Cellular Senescence/genetics, Carbon/metabolism, Female, ddc:570, Glycolysis
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