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Nature communications
10 01, 2018;9 (1): 4004.

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
  1. Marco L Hennrich: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
  2. Natalie Romanov: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
  3. Patrick Horn: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany.
  4. Samira Jaeger: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, 08028, Catalonia, Spain.
  5. Volker Eckstein: Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany.
  6. Violetta Steeples: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK.
  7. Fei Ye: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
  8. Ximing Ding: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
  9. Laura Poisa-Beiro: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany.
  10. Mang Ching Lai: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany.
  11. Benjamin Lang: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
  12. Jacqueline Boultwood: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK.
  13. Thomas Luft: Department of Medicine V, Heidelberg University, Heidelberg, D69120, Germany.
  14. Judith B Zaugg: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
  15. Andrea Pellagatti: Radcliffe Department of Medicine, University of Oxford and Oxford BRC Haematology Theme, Oxford, OX3 9DU, UK. ORCID
  16. Peer Bork: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. ORCID
  17. Patrick Aloy: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, 08028, Catalonia, Spain.
  18. Anne-Claude Gavin: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg, D69117, Germany. gavin@embl.de.
  19. Anthony D Ho: Molecular Medicine Partnership Unit (MMPU), Meyerhofstrasse 1, Heidelberg, D69117, Germany. anthony_dick.ho@urz.uni-heidelberg.de. ORCID
PMID: 30275468 DOI: 10.1038/s41467-018-06353-4

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.

References

  1. Cell Rep. 2016 Oct 18;17(4):1037-1052 [PMID: 27760311]
  2. Nat Commun. 2016 Mar 24;7:11075 [PMID: 27009448]
  3. Nat Cell Biol. 2017 Apr;19(4):271-281 [PMID: 28319093]
  4. Curr Biol. 1997 Oct 1;7(10):805-8 [PMID: 9368765]
  5. Nat Med. 2012 Sep;18(9):1350-8 [PMID: 22902876]
  6. J Exp Med. 2011 Mar 14;208(3):421-8 [PMID: 21402747]
  7. Blood. 2005 Dec 15;106(13):4034-42 [PMID: 16051738]
  8. Bone Marrow Res. 2011;2011:353878 [PMID: 22046560]
  9. Blood. 2005 Aug 15;106(4):1479-87 [PMID: 15827136]
  10. Exp Gerontol. 2008 Nov;43(11):974-80 [PMID: 18504082]
  11. Nature. 2003 Oct 23;425(6960):841-6 [PMID: 14574413]
  12. Nat Commun. 2015 Jul 22;6:7866 [PMID: 26198319]
  13. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20012-7 [PMID: 22123971]
  14. Nat Protoc. 2014 Jan;9(1):171-81 [PMID: 24385147]
  15. Science. 2015 Jan 23;347(6220):1260419 [PMID: 25613900]
  16. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  17. PLoS One. 2016 Jan 04;11(1):e0144561 [PMID: 26727002]
  18. Nature. 2014 May 29;509(7502):582-7 [PMID: 24870543]
  19. Mol Cell. 2016 Jan 21;61(2):210-21 [PMID: 26774282]
  20. Nat Med. 1996 Sep;2(9):1011-6 [PMID: 8782459]
  21. Biochem Biophys Res Commun. 1967 Jan 23;26(2):162-7 [PMID: 6030262]
  22. Cell Rep. 2013 May 30;3(5):1714-24 [PMID: 23623496]
  23. Cell Syst. 2015 Sep 23;1(3):224-37 [PMID: 27135913]
  24. Nat Med. 2015 Dec;21(12):1416-23 [PMID: 26646498]
  25. J Exp Med. 2011 Dec 19;208(13):2691-703 [PMID: 22110168]
  26. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  27. Blood. 2010 Dec 2;116(23):4815-28 [PMID: 20713966]
  28. Br J Haematol. 1999 Mar;104(4):801-8 [PMID: 10192443]
  29. BMC Bioinformatics. 2014 Jun 12;15:182 [PMID: 24925680]
  30. PLoS One. 2009 Jun 09;4(6):e5846 [PMID: 19513108]
  31. J Biol Chem. 2015 Sep 4;290(36):22174-83 [PMID: 26198639]
  32. Nature. 2010 Aug 12;466(7308):829-34 [PMID: 20703299]
  33. PLoS One. 2008 May 21;3(5):e2213 [PMID: 18493317]
  34. Nat Methods. 2016 Jul;13(7):577-80 [PMID: 27240256]
  35. Int J Hematol. 2014 Oct;100(4):317-25 [PMID: 25096220]
  36. Nucleic Acids Res. 2013 May 1;41(10):e108 [PMID: 23558742]
  37. Nat Immunol. 2010 Jul;11(7):585-93 [PMID: 20543838]
  38. J Exp Med. 2000 Nov 6;192(9):1273-80 [PMID: 11067876]
  39. Nat Biotechnol. 2008 Dec;26(12):1367-72 [PMID: 19029910]
  40. Science. 2009 May 22;324(5930):1029-33 [PMID: 19460998]
  41. Mech Ageing Dev. 2001 Sep 30;122(14):1537-53 [PMID: 11511395]
  42. Nat Genet. 2011 Jul 31;43(9):869-74 [PMID: 21804546]
  43. Blood Cells. 1978;4(1-2):7-25 [PMID: 747780]
  44. J Inherit Metab Dis. 2010 Oct;33(5):469-77 [PMID: 20195903]
  45. G3 (Bethesda). 2018 Jan 4;8(1):79-89 [PMID: 29118030]
  46. Ann Hematol. 2016 Oct;95(10):1571-82 [PMID: 26983918]
  47. F1000Res. 2015 Dec 30;4:1521 [PMID: 26925227]
  48. Cytotherapy. 2006;8(4):315-7 [PMID: 16923606]
  49. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9194-9 [PMID: 15967997]
  50. J Exp Med. 2013 Jul 1;210(7):1351-67 [PMID: 23776077]
  51. F1000Res. 2016 Aug 31;5:2122 [PMID: 27909575]
  52. Development. 2013 Jun;140(12):2535-47 [PMID: 23715547]
  53. J Biol Chem. 2004 Nov 12;279(46):48350-9 [PMID: 15339928]
  54. Aging Cell. 2010 Feb;9(1):54-63 [PMID: 19895632]
  55. Nat Rev Drug Discov. 2016 Mar;15(3):173-83 [PMID: 26822833]
  56. Cell Stem Cell. 2009 Oct 2;5(4):442-9 [PMID: 19796624]
  57. J Reprod Dev. 2012;58(6):691-9 [PMID: 22972184]
  58. Nat Methods. 2015 Apr;12(4):357-60 [PMID: 25751142]
  59. Leukemia. 2009 Feb;23(2):391-3 [PMID: 18596738]
  60. Cell Stem Cell. 2010 Mar 5;6(3):265-78 [PMID: 20207229]
  61. Nucleic Acids Res. 2017 Jan 4;45(D1):D362-D368 [PMID: 27924014]
  62. Nature. 2011 May 19;473(7347):337-42 [PMID: 21593866]
  63. J Exp Biol. 2003 Jun;206(Pt 12):2049-57 [PMID: 12756287]
  64. Nat Methods. 2017 Apr;14(4):417-419 [PMID: 28263959]
  65. Genome Biol. 2016 Mar 14;17:47 [PMID: 26975353]
  66. Nat Rev Immunol. 2013 May;13(5):376-89 [PMID: 23584423]
  67. Mol Ther. 2004 Aug;10(2):241-8 [PMID: 15294171]
  68. Stem Cells Int. 2015;2015:762098 [PMID: 26236348]
  69. Exp Hematol. 2017 Jun;50:22-26 [PMID: 28189651]
  70. Anal Chem. 2003 Apr 15;75(8):1895-904 [PMID: 12713048]
  71. Free Radic Biol Med. 2011 Dec 15;51(12):2150-7 [PMID: 22019632]
  72. J Exp Med. 2011 Feb 14;208(2):261-71 [PMID: 21282381]
  73. Cytotherapy. 2012 Feb;14(2):135-43 [PMID: 22107161]
  74. Cell Rep. 2016 Oct 11;17(3):821-836 [PMID: 27732857]
  75. Nat Med. 2014 Aug;20(8):833-46 [PMID: 25100529]
  76. Nature. 2009 Jan 1;457(7225):92-6 [PMID: 19052546]
  77. Blood. 2001 Oct 15;98(8):2403-11 [PMID: 11588037]

Grants

  1. /Wellcome Trust

MeSH Term

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

Chemicals

Proteome
Carbon
Comparative Study Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000049 (Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline [single cells])

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