Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline.
Marco L Hennrich, Natalie Romanov, Patrick Horn, Samira Jaeger, Volker Eckstein, Violetta Steeples, Fei Ye, Ximing Ding, Laura Poisa-Beiro, Mang Ching Lai, Benjamin Lang, Jacqueline Boultwood, Thomas Luft, Judith B Zaugg, Andrea Pellagatti, Peer Bork, Patrick Aloy, Anne-Claude Gavin, Anthony D Ho
Author Information
- Marco L Hennrich: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
- Natalie Romanov: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
- Patrick Horn: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany.
- Samira Jaeger: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, 08028, Catalonia, Spain.
- Volker Eckstein: Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany.
- Violetta Steeples: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK.
- Fei Ye: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
- Ximing Ding: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
- Laura Poisa-Beiro: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany.
- Mang Ching Lai: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
- Benjamin Lang: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
- Jacqueline Boultwood: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK.
- Thomas Luft: Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany.
- Judith B Zaugg: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
- Andrea Pellagatti: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK. ORCID
- Peer Bork: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
- Patrick Aloy: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, 08028, Catalonia, Spain.
- Anne-Claude Gavin: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. gavin@embl.de.
- Anthony D Ho: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany. anthony_dick.ho@urz.uni-heidelberg.de. ORCID
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.
Adult
Adult Stem Cells
Aging
Bone Marrow Cells
Carbon
Cellular Senescence
Female
Gene Expression Profiling
Glycolysis
Hematopoiesis
Hematopoietic Stem Cells
Humans
Male
Middle Aged
Proteome
Stem Cell Niche
Young Adult
