Functional effects of DNMT3A R882 on human haematopoietic stem and progenitor cells myeloid differentiation

This data presents the transcriptomes of bulk mature colonies derived from single human haematopoietic stem cells / multipotent progenitors (HSC/MPPs) and granulocyte macrophage progenitors (GMPs) purified from one indiviual with age related clonal haematopoisesis. The profiled colonies contain mature monocytes, as measured by conventional cell surface markers (CD14+, CD15-, GlyA-), but no other mature blood cell types. This dataset is part of a larger study, the main objective of which is to understand the functional effects conferred by somatic DNMT3A R882H mutation on human haematopoietic stem cell differentiation capacity. In clonal haematopoiesis, DNMT3A R882H and DNMT3A WT HSPCs co-exist in the same individual. We compared the transcriptional differences between mature monocytic colonies derived from DNMT3A R882H and WT HSPCs in vitro. Analysis of this dataset shows that, in this individual, DNMT3A R882H HSPCs produce less mature monocytes than their WT counterparts over the same culture time. Overall design: 39 bulk monocyte colonies derived from 33 single HSC/MPPs and 6 single GMPs were analysed from 1 individual. Single HSC/MPPs (CD19-, CD33-, CD34+, CD45dim, CD38-, CD45RA+), and GMPs (CD19-, CD33-, CD34+, CD45dim, CD38+, CD7/CD10-, CD45RA+) were cultured in vitro for 21 days in myelo-erythroid medium (MEM), colonies containing mature monocytes but no other mature blood cell lineage were selected and harvested into RNA extraction plates and RNA extracted using the Qiagen RNeasy protocol.