Author response: An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability

Abstract

Transcription factor (TF) networks determine cell-type identity by establishing and maintaining lineage-specific expression profiles, yet reconstruction of mammalian regulatory network models has been hampered by a lack of comprehensive functional validation of regulatory interactions. Here, we report comprehensive ChIP-Seq, transgenic and reporter gene experimental data that have allowed us to construct an experimentally validated regulatory network model for haematopoietic stem/progenitor cells (HSPCs). Model simulation coupled with subsequent experimental validation using single cell expression profiling revealed potential mechanisms for cell state stabilisation, and also how a leukaemogenic TF fusion protein perturbs key HSPC regulators. The approach presented here should help to improve our understanding of both normal physiological and disease processes.

Spatial Genome Re-organization between Fetal and Adult Hematopoietic Stem Cells

“…To further confirm if TCF3 can mediate developmental-stagespecific enhancer-promoter interactions, we performed Capture-C experiment comparing wild-type HPC-7 cells and HPC-7 cells with Tcf3 knockout using CRISPR-Cas9 technology (Figure 4D). HPC-7 is a murine multi-potent hematopoietic precursor cell line that has been used as a model of HSCs (Pinto do O, et al, 1998;Sch€ utte et al, 2016;Wilson et al, 2010). Tcf3 knockout has a modest effect on the overall cell cycle duration of HPC-7 cells (Figures S7A-S7C).…”