TY  - JOUR
A1  - Hennrich, Marco L.
A1  - Romanov, Natalie
A1  - Horn, Patrick
A1  - Jaeger, Samira
A1  - Eckstein, Volker
A1  - Steeples, Violetta
A1  - Ye, Fei
A1  - Ding, Ximing
A1  - Poisa-Beiro, Laura
A1  - Mang, Ching Lai
A1  - Lang, Benjamin
A1  - Boultwood, Jacqueline
A1  - Luft, Thomas
A1  - Zaugg, Judith B.
A1  - Pellagatti, Andrea
A1  - Bork, Peer
A1  - Aloy, Patrick
A1  - Gavin, Anne-Claude
A1  - Ho, Anthony D.
T1  - Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
JF  - Nature Communications
N2  - 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.
KW  - ageing
KW  - haematopoietic stem cells
KW  - mesenchymal stem cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319877
VL  - 9
ER  -