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Nat Commun. 2018 Oct 1;9(1):4004. doi: 10.1038/s41467-018-06353-4.

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

Author information

1
European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
2
Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany.
3
Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany.
4
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, 08028, Catalonia, Spain.
5
Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK.
6
Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, D97074, Germany.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08010, Catalonia, Spain.
8
European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. gavin@embl.de.
9
Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany. gavin@embl.de.
10
Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany. anthony_dick.ho@urz.uni-heidelberg.de.
11
Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany. anthony_dick.ho@urz.uni-heidelberg.de.

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.

PMID:
30275468
PMCID:
PMC6167374
DOI:
10.1038/s41467-018-06353-4
[Indexed for MEDLINE]
Free PMC Article

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