title: Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
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.
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Amit
authors.initials: A
authors.lastname: Grover
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sanjuan-Pla
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Supat
authors.initials: S
authors.lastname: Thongjuea
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Joana
authors.initials: J
authors.lastname: Carrelha
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Giustacchini
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH16 4UU, UK.|EMBL Mouse Biology Program, 00015 Monterotondo, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Macaulay
authors.affiliation: EMBL Mouse Biology Program, 00015 Monterotondo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Mancini
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Tiago C
authors.initials: TC
authors.lastname: Luis
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Mead
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.|Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH16 4UU, UK.|EMBL Mouse Biology Program, 00015 Monterotondo, Italy.
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D016922:Cellular Senescence; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse