A pro B cell population forms the apex of the leukemic hierarchy in Hoxa9/Meis1-dependent AML

In the murine HoxA9/Meis1 (H9M) AML model leukemic stem cell (LSC) potential lies in three different heterogeneous immunophenotypes including Lin-cKit+ progenitor cells (Lin-), Gr1+CD11b+cKit+ myeloid cells and lymphoid cells (Lym+). We performed scRNA-seq to reveal the cell type contribution of HoxA9/Meis1 bone marrow and the hierarchical organization of different immunophenotypes. Therefore, primary and secondary bone marrow of HoxA9/Meis1 tranplanted animals were isolated, sorted and sequenced. We could identify that in the HoxA9/Meis1 AML model a pro-B cell population resides at the apex. In total, 3 bone marrow samples from 3 HoxA9/Meis1 mice were analyzed. 1 sample contained bone marrow from a primary recipient and two samples contained bone marrow from its secondary recipiemts transplanted with Lin- and Lym+ LSCs. For parallel sequencing, the samples were labeled with hashtag probes: primary HoxA9/Meis1 bone marrow (Hash #4), secondary bone marrow tranplanted with Lin- LSCs (Hash #5), and secondary bone marrow transplanted with Lym+ LSCs (Hash #6).