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

• Published in: Nature communications Vol. 9; no. 1; pp. 4004 - 18
• Main Authors: Hennrich, Marco L., Romanov, Natalie, Horn, Patrick, Jaeger, Samira, Eckstein, Volker, Steeples, Violetta, Ye, Fei, Ding, Ximing, Poisa-Beiro, Laura, Lai, Mang Ching, Lang, Benjamin, Boultwood, Jacqueline, Luft, Thomas, Zaugg, Judith B., Pellagatti, Andrea, Bork, Peer, Aloy, Patrick, Gavin, Anne-Claude, Ho, Anthony D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/91; 631/532/1542; 631/532/2074; 631/532/7; 82/58; Adult; Adult Stem Cells - cytology; Aging; Aging - genetics; Aging - metabolism; Aging - pathology; Animal models; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Carbon - metabolism; Cells (biology); Cellular Senescence - genetics; Differentiation; Female; Gene Expression Profiling; Glycolysis; Hematopoiesis; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Homing; Humanities and Social Sciences; Humans; Intermediates; Male; Metabolism; Middle Aged; multidisciplinary; Niches; Progenitor cells; Proteins; Proteome; Proteomes; Regulators; Science; Science (multidisciplinary); Stem Cell Niche; Stem cell transplantation; Stem cells; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06353-4

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.