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Single-cell analysis identifies a CD33+ subset of human cord blood cells with high regenerative potential

Elucidation of the identity and diversity of mechanisms that sustain long-term human blood cell production remains an important challenge. Previous studies indicate that, in adult mice, this property is vested in cells identified uniquely by their ability to clonally regenerate detectable, albeit highly variable levels and types, of mature blood cells in serially transplanted recipients. From a multi-parameter analysis of the molecular features of very primitive human cord blood cells that display long-term cell outputs in vitro and in immunodeficient mice, we identified a prospectively separable CD33+CD34+CD38−CD45RA−CD90+CD49f+ phenotype with serially transplantable, but diverse, cell output profiles. Single-cell measurements of the mitogenic response, and the transcriptional, DNA methylation and 40-protein content of this and closely related phenotypes revealed subtle but consistent differences both within and between each subset. These results suggest that multiple regulatory mechanisms combine to maintain different cell output activities of human blood cell precursors with high regenerative potential.

Authors:   David J. H. F. Knapp; Colin A. Hammond; Tony Hui; Marijn T. J. Loenhout; Fangwu Wang; Nima Aghaeepour; Paul H. Miller; Michelle Moksa; Gabrielle M. Rabu; Philip A. Beer; Davide Pellacani; R. Keith Humphries; Carl Hansen; Martin Hirst; Connie J. Eaves
Journal:   Nature Cell Biology
Volume:   20
edition:   6
Year:   2018
Pages:   710
DOI:   10.1038/s41556-018-0104-5
Publication date:   25-May-2018
Facts, background information, dossiers
  • cord blood
  • blood
  • single cell analysis
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