Normal hematopoietic stem and progenitor cells in murine acute myeloid leukemia model in vivo
Bone marrow inflammation has been linked to acute myeloid leukemia (AML) progression. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche, but the involvment of normal hematopoietic stem and progenitor cells (HSPCs) in the inflammatory crosstalk is not well understood. To better model compartmental inflammation in AML, we first established a highly penetrant, immunocompetent, fully congenic system. Using the monoblastic AML cell line C1498 (CD45.2+), we grafted non-condition C57BL/6J (CD45.1) mice, avoiding changes in BM niche function. We then fluoresence-activated cell sorting (FACS)-sorted residual normal HSPCs for single-cell RNA-sequencing analysis. We show that residual normal HSPCs from C1498-grafted mice expresses key inflammatory signature and are enriched in inflammatory signaling related pathways. Overall, we show that normal HSPCs engages in inflammatory signaling in AML niche. Overall design: C1498 mice were generated by injecting C1498 cells (CD45.2; 1E6 cells per recipient) into healthy non-conditioned C57BL/6J mice (CD45.1; 8-12 weeks; female; Jacksons Laboratory). PBS-injected mice serve as control. Mice were sacrificed 21-day after injection. Bone marrow hematopoietic stem and progenitor cells (HSPCs; CD45.1+ Lin- cKit+ Sca1+) were fluorescent-activated cell sorting (FACS)-sorted for gene expression assay.