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Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
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Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
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Journal Article
Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
2018
Overview
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.
Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/91
/ 82/58
/ Adult
/ Aging
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - metabolism
/ Cellular Senescence - genetics
/ Female
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Homing
/ Humanities and Social Sciences
/ Humans
/ Male
/ Niches
/ Proteins
/ Proteome
/ Science
