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

Amit Grover, Alejandra Sanjuan-Pla, Supat Thongjuea, Joana Carrelha, Alice Giustacchini, Adriana Gambardella, Iain Macaulay, Elena Mancini, Tiago C. Luis, Adam Mead, Sten Eirik W. Jacobsen () and Claus Nerlov ()
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Amit Grover: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Alejandra Sanjuan-Pla: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Supat Thongjuea: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Joana Carrelha: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Alice Giustacchini: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Adriana Gambardella: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Iain Macaulay: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Elena Mancini: EMBL Mouse Biology Program
Tiago C. Luis: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Adam Mead: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Sten Eirik W. Jacobsen: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Claus Nerlov: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11075

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