Comprehensive Proteomic Characterization of Ontogenic Changes in Hematopoietic Stem and Progenitor Cells

Cell Rep. 2017 Dec 12;21(11):3285-3297. doi: 10.1016/j.celrep.2017.11.070.

Abstract

Hematopoietic stem and progenitor cells (HSPCs) in the fetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of hematopoietic malignancies. Here, we applied in-depth quantitative proteomics to comprehensively describe and compare the proteome of fetal and adult HSPCs. Our data uncover a striking difference in complexity of the cellular proteomes, with more diverse adult-specific HSPC proteomic signatures. The differential protein content in fetal and adult HSPCs indicate distinct metabolic profiles and protein complex stoichiometries. Additionally, adult characteristics include an arsenal of proteins linked to viral and bacterial defense, as well as protection against ROS-induced protein oxidation. Further analyses show that interferon α, as well as Neutrophil elastase, has distinct functional effects in fetal and adult HSPCs. This study provides a rich resource aimed toward an enhanced mechanistic understanding of normal and malignant hematopoiesis during fetal and adult life.

Keywords: developmental hematopoiesis; hematopoiesis; hematopoietic stem cells; proteomics.

MeSH terms

  • Age Factors
  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Embryo, Mammalian
  • Fetus
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism
  • Leukocyte Elastase / genetics
  • Leukocyte Elastase / metabolism
  • Mice, Inbred C57BL
  • Proteome / genetics*
  • Proteome / metabolism
  • Proteomics / methods

Substances

  • Interferon-alpha
  • Proteome
  • Leukocyte Elastase