Proteomic Cornerstones of Hematopoietic Stem Cell Differentiation: Distinct Signatures of Multipotent Progenitors and Myeloid Committed Cells

• DOI: 10.1074/mcp.m111.016790
• Publication Date: 2012-03-29T00:33:57Z
• Authors: Daniel Klimmeck; Jenny Hansson; Simon Raffel; Sergey Y. Vakhrushev; Andreas Trumpp; Jeroen Krijgsveld
• Keywords: Multipotent Stem Cell; Proteome

Regenerative tissues such as the skin epidermis, intestinal mucosa or hematopoietic system are organized in a hierarchical manner with stem cells building top of this hierarchy. Somatic harbor highest self-renewal activity and generate series multipotent progenitors which differentiate into lineage committed subsequently mature cells. In report, we applied an in-depth quantitative proteomic approach to analyze compare full proteomes ex vivo isolated FACS-sorted populations highly enriched for either stem/progenitor (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) myeloid precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling high-resolution mass spectrometry, more than 5000 proteins were quantified. From biological triplicate experiments subjected rigorous statistical evaluation, 893 found differentially expressed between The differential protein content these cell points distinct structural organization cytoskeleton including remodeling activity. addition, marked difference expression metabolic enzymes, clear shift specific isoforms glycolytic pathway. Proteins involved translation showed collective higher progenitors, indicating increased translational Strikingly, data uncover unique signature related immune defense mechanisms, centering on RIG-I type-1 interferon response systems, installed but not evident This suggests that specific, so far unrecognized, mechanisms protect immature before they mature. conclusion, study indicates transition stem/progenitors toward commitment is accompanied by profound change processing cellular resources, adding novel insights molecular at interface multipotency commitment.