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Study Uses Single-Cell Proteomics to Map Early Human Blood Differentiation

Direct protein measurements reveal regulation missed by RNA-only methods.

Overview

  • The Science paper applies single-cell proteomics by mass spectrometry to primary human CD34+ bone marrow cells, marking the first use of this approach in a biologically relevant human system.
  • Researchers profiled more than 2,500 hematopoietic stem and progenitor cells and integrated scp-MS with scRNA-seq to build a dynamic view of gene expression across differentiation.
  • mRNA and protein levels aligned in more differentiated blood cells but diverged in stem and immature cells, pointing to shifts in mRNA turnover, translation, or protein stability during maturation.
  • Proteins that declined at the protein level despite stable mRNA proved essential for maintaining stem cell populations, as gene knock-outs reduced stem cell numbers.
  • The technology was co-developed by DTU, Rigshospitalet, and the University of Copenhagen, with authors noting future gains in sensitivity are needed for fuller proteome coverage and broader biomedical applications.