LMO2 Is Required for TAL1 DNA Binding Activity and Initiation of Definitive Haematopoiesis at the Haemangioblast Stage. Mus musculus

We differentiated WT, LMO2KO or TAL1 KO mouse ES cell lines into Flk-1+ haemangioblasts and/or Tie2+;Kit+;CD41- haemogenic endothelium 1 (HE1). We performed RNAseq, ChIPseq and/or DHS seq on these cells and compared the samples. Our study showed that Lmo2-/- embryonic stem cells differentiated less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. LMO2 was required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program. In the absence of LMO2, TAL1 protein levels were low and the target site recognition of TAL1 was impaired. Overall design: RNAseq (paired end) of WT, LMO2KO or TAL1KO Flk-1+ haemangioblasts in triplicates and WT, LMO2KO Tie2+;Kit+;CD41- haemogenic endothelium 1 (HE1) in duplicate. ChIPseq, using aLMO2, aTAL1, aLDB1 antibodies, of WT, LMO2KO Flk-1+ haemangioblasts in duplicates. DHSseq on WT, LMO2KO Flk-1+ haemangioblasts.