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Scientific article
Open access
English

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

Published inNature Communications, vol. 9, no. 1, 4004
Publication date2018
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.

Keywords
  • Adult
  • Adult Stem Cells/cytology
  • Aging/genetics/metabolism/pathology
  • Bone Marrow Cells/cytology/metabolism
  • Carbon/metabolism
  • Cellular Senescence/genetics
  • Female
  • Gene Expression Profiling
  • Glycolysis
  • Hematopoiesis
  • Hematopoietic Stem Cells/cytology/metabolism
  • Humans
  • Male
  • Middle Aged
  • Proteome
  • Stem Cell Niche
  • Young Adult
Affiliation Not a UNIGE publication
Funding
  • Autre - Problem conditioning in convex optimization: theory and algorithms [0306240]
Citation (ISO format)
HENNRICH, Marco L et al. Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline. In: Nature Communications, 2018, vol. 9, n° 1, p. 4004. doi: 10.1038/s41467-018-06353-4
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal2041-1723
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208downloads

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