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

• Published in: Nature communications Vol. 7; no. 1; p. 11075
• Main Authors: Grover, Amit, Sanjuan-Pla, Alejandra, Thongjuea, Supat, Carrelha, Joana, Giustacchini, Alice, Gambardella, Adriana, Macaulay, Iain, Mancini, Elena, Luis, Tiago C, Mead, Adam, Jacobsen, Sten Eirik W, Nerlov, Claus
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 24.03.2016; Nature Portfolio
• Subjects: Animals; Blood Platelets - metabolism; Cell Lineage - genetics; Cell Proliferation; Cellular Senescence; Female; Gene Expression Profiling; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Male; Medicin och hälsovetenskap; Mice; Myeloid Cells - cytology; Nuclear Proteins - metabolism; Phenotype; Sequence Analysis, RNA - methods; Single-Cell Analysis - methods; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11075

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.