Impact of Tle1, Tle3, and Tle4 deficiency on hematopoietic stem cells (HSCs) [RNA-seq]

To compare the transcriptomes between control and Tle1/3/4-deficient HSCs Tle co-repressors can co-opt a number of transcription factors to repress target gene expression. Due to gene duplication during evolution, there are 4 Tle genes in mammalian genome, and their functional redundancy has a major hurdle to understand their roles in hematopoietic stem cells (HSCs). Here we used Vav-Cre to ablate Tle1, 3, and 4 genes in HSCs, and performed RNA-seq to determine the impact of Tle deficiency on HSCs. To further define the regulatory mechanisms, we performed Tle3 ChIPseq on c-Kit+ hematopoietic progenitor cells. The data obtained collectively indicate a critical, intrinsic requirement for Tle corepressors in HSC self-renewal. Overall design: Bone marrow cells were harvested from control or Tle1/3/4-deficient mice. For the latter, all three Tle genes were floxed, and Vav-Cre was used to excise the floxed genes in all hematopoietic cells including HSCs. Lin-cKit+Sca1+ CD150+CD48– HSCs were sort-purified for total RNA extraction.