Single cell transcriptome level assessment of human platelet-biased hematopoietic stem cells isolated from bone marrow samples obtained from healthy young and old adult donors.

Functional heterogeneity of hematopoietic stem cells (HSCs) heterogeneity has been extensively described in mice, but so far not described in human bone marrow (BM). In particular, HSCs biased towards platelet formation have been identified, and shown to be expanded during ageing and implicated as cells-of-origin for essential thrombocythemia (ET). By combining xenografting of molecularly barcoded adult human BM HSCs and high-throughput single cell RNA sequencing we here identify human BM HSCs that are molecularly and functionally platelet-biased. Furthermore, a quantitative comparison of transcriptomes from young and aged BM HSCs showed that both the proportion of platelet-biased HSCs and their level of molecular platelet priming increases with age. Examination of the transcriptome of single cell human bone marrow HSCs (Lin–CD34+CD38–CD90+CD45RA–) from healthy adult young (21-24yo) and old (68-75yo) donors.