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

Author

Listed:
  • Marco L. Hennrich

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU))

  • Natalie Romanov

    (Structural and Computational Biology Unit)

  • Patrick Horn

    (Molecular Medicine Partnership Unit (MMPU)
    Heidelberg University)

  • Samira Jaeger

    (The Barcelona Institute of Science and Technology)

  • Volker Eckstein

    (Heidelberg University)

  • Violetta Steeples

    (University of Oxford and Oxford BRC Haematology Theme)

  • Fei Ye

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU))

  • Ximing Ding

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU)
    Heidelberg University)

  • Laura Poisa-Beiro

    (Molecular Medicine Partnership Unit (MMPU)
    Heidelberg University)

  • Mang Ching Lai

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU))

  • Benjamin Lang

    (Structural and Computational Biology Unit)

  • Jacqueline Boultwood

    (University of Oxford and Oxford BRC Haematology Theme)

  • Thomas Luft

    (Heidelberg University)

  • Judith B. Zaugg

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU))

  • Andrea Pellagatti

    (University of Oxford and Oxford BRC Haematology Theme)

  • Peer Bork

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU)
    University of Würzburg)

  • Patrick Aloy

    (The Barcelona Institute of Science and Technology
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Anne-Claude Gavin

    (Structural and Computational Biology Unit
    Molecular Medicine Partnership Unit (MMPU))

  • Anthony D. Ho

    (Molecular Medicine Partnership Unit (MMPU)
    Heidelberg University)

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.

Suggested Citation

  • 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 Boultw, 2018. "Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06353-4
    DOI: 10.1038/s41467-018-06353-4
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