Targeting fatty acid metabolism to abrogate differentiation block in pre-leukemia induced by AML1-ETO [2]

To gain the underlying insight into the functional impact of AML1-ETO expressed in hematopoietic stem cells and progenitors (HSPCs), we employed single-cell transcriptome sequencing to elucidate the characteristics of purified Lin-c-kit+ cells (HSPCs) from the bone marrow (BM) of both AML1-ETO expressed (AML1/ETO) and Wild-Type (control) C57 mice. The conditional inducible knock-in C57BL/6 murine model was established with an inducible Cre recombinase (Mx1-Cre) and heterozygous conditional knock-in of Runx1-Run1t1 in hematopoietic system. Mice with the Runx1-Runx1t1 genotype carry the mCherry sequence downstream of the Runx1-Runx1t1 sequence. Upon Poly[I:C] induction, the Runx1-Runx1t1 protein with mCherry fluorescence will be expressed (mCherry+) , while cells which have not responsed by Poly[I:C] will not express Runx1-Runx1t1 protein and fluoresce without mCherry (non_mCherry). Single-cell RNA-seq was performed on purified Lin-c-kit+ cells from the bone marrow (BM) of both AML1-ETO expressed (AML1/ETO) and Wild-Type (control) C57 mice.The BM cells were sorted using AriaIII as follows: DAPI-Lin-c-kit+ cells from the control mouse, DAPI-mCherry-Lin-c-kit+ cells from the AML1/ETO mouse (non-mCherry group) and DAPI-mCherry+Lin-c-kit+ cells from the AML1/ETO mouse (mCherry+ group). And the cells of non-mCherry group and mCherry+ group were derived from the same AML1/ETO mouse.