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Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline

Authors: Hennrich, M; Romanov, N; Horn, P; Jaeger, S; Eckstein, V; Steeples, V; Ye, F; +12 Authors

Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline

Abstract

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.

Countries
Switzerland, United Kingdom, Germany
Keywords

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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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    impulse
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    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
86
Top 1%
Top 10%
Top 1%
Green
gold