Abstract

The process of hematopoiesis is subject to substantial ontogenic remodeling that is accompanied by alterations in cellular fate during both development and disease. We combine state-of-the-art mass spectrometry with extensive functional assays to gain insight into ontogeny-specific proteomic mechanisms regulating hematopoiesis. Through deep coverage of the cellular proteome of fetal and adult lympho-myeloid multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs), and granulocyte-monocyte progenitors (GMPs), we establish that features traditionally attributed to adult hematopoiesis are conserved across lymphoid and myeloid lineages, whereas generic fetal features are suppressed in GMPs. We reveal molecular and functional evidence for a diminished granulocyte differentiation capacity in fetal LMPPs and GMPs relative to their adult counterparts. Our data indicate an ontogeny-specific requirement of myosin activity for myelopoiesis in LMPPs. Finally, we uncover an ontogenic shift in the monocytic differentiation capacity of GMPs, partially driven by a differential expression of Irf8 during fetal and adult life.

Original languageEnglish
Article number108894
JournalCell Reports
Volume34
Issue number12
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Hematology

Keywords

  • Adult Stem Cells/cytology
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Fetus/cytology
  • Granulocytes/cytology
  • HEK293 Cells
  • Hematopoietic Stem Cells/cytology
  • Humans
  • Immunophenotyping
  • Interferon Regulatory Factors/metabolism
  • Kinetics
  • Lymphoid Progenitor Cells/cytology
  • Mice, Inbred C57BL
  • Monocytes/cytology
  • Myeloid Progenitor Cells/cytology
  • Proteome/metabolism
  • Proteomics
  • rho-Associated Kinases/antagonists & inhibitors

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