GSE158827
Single-cell RNASeq analysis to unravel molecular networks driving leukemia in Ebf1+/-Pax5+/- (dHet) B-ALL mice
Here, we report that EBF1 and Pax5 collaborate in a  dose-dependent manner to regulate the IL-7-STAT5 signaling  pathway and one-carbon metabolism, whereby  we found both diminished and enhanced binding of  EBF1 and Pax5 to target genes in compound heterozygous  mutant mice. Moreover, single-cell RNA sequencing  analysis identified a small subset of wild-type pro-B cells  on the trajectory to pre-B cells that share gene expression  signatures with leukemic Ebf1+/-Pax5+/- pro-B cells.  Thus, a normal expression level of EBF1 and Pax5 is required  for safeguarding a potentially vulnerable pro-Bcell  subset from a transformation to B-ALL. Overall design: Single cells from the bone marrow, spleen or blood were sorted into 384-well plates and processed using a modified version of the CEL-Seq2 protocol (Hasimshony et al. 2016, Genome Biology, DOI: 10.1186/s13059-016-0938-8).