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

Autor: Michelle Moksa, Paul H. Miller, Martin Hirst, Fangwu Wang, Philip A. Beer, Tony Hui, R. Keith Humphries, Connie J. Eaves, Colin A. Hammond, Davide Pellacani, Nima Aghaeepour, Carl L. Hansen, Gabrielle Rabu, Marijn T J van Loenhout, David J.H.F. Knapp
Rok vydání: 2018
Předmět:
Zdroj: Nature Cell Biology. 20:710-720
ISSN: 1476-4679
1465-7392
DOI: 10.1038/s41556-018-0104-5
Popis: 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.
Databáze: OpenAIRE
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