Hematopoietic stem cells (HSC) reconstitute multi-lineage human hematopoiesis after clinical bone marrow transplantation and are the cells-of-origin of hematological malignancies. Though HSC provide multi-lineage engraftment, individual murine HSCs are lineage-biased and contribute unequally to blood cell lineages. Now, by combining xenografting of molecularly barcoded adult human bone marrow (BM) HSCs and high-throughput single cell RNA sequencing we demonstrate that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identify platelet-biased and multi-lineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young, and aged, BM show that both the proportion of platelet-biased HSCs, and their level of transcriptional platelet priming, increases with age. Therefore, platelet-biased HSCs, as well as their increased prevalence and elevated transcriptional platelet priming during ageing, are conserved between human and murine hematopoiesis.
Efficient Transcriptional Targeting of Human Hematopoietic Stem Cells and Blood Cell Lineages by Lentiviral Vectors Containing the Regulatory Element of the Wiskott-Aldrich Syndrome Gene