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Nat Commun. 2016 Mar 24;7:11075. doi: 10.1038/ncomms11075.

Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.

Author information

1
MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
2
Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH16 4UU, UK.
3
Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
4
EMBL Mouse Biology Program, 00015 Monterotondo, Italy.

Abstract

Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis.

PMID:
27009448
PMCID:
PMC4820843
DOI:
10.1038/ncomms11075
[Indexed for MEDLINE]
Free PMC Article

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