Overexpression of human TLR8 alters the bone marrow erythropoietic niche and causes fatal anemia in SLE-prone mice

The goal of this study was to understand the cause of anemia in lupus prone mice expressing humn TLR8. This was found to be due to a block in erythroblast differentiation form the CFUE to proerythroblast stage, a step that occurs within erythroblastic islands. We analyzed 19,309 bone marrow EBI cells and 4,794 spleen EBI cells that formed 22 clusters of cells. We confirmed the block in CFUE differentiation and found a defect in central macrophages that caused failure of erythroblast adherence We compared sequences of single cells from isolated and dissociated bone marrow and spleen erythroblastic islands from male lupus prone mice (Sle1.Yaa) expressing a human TLR8 transgene with sequences of single cells from isolated bone marrow erythroblastic islands from Sle1.Yaa controls using 10X genomics V3.1 platform