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

Judith Schütte, Huange Wang, Stella Antoniou, Andrew Jarratt, Nicola K Wilson, Joey Riepsaame, Fernando J Calero-Nieto, Victoria Moignard, Silvia Basilico, Sarah J Kinston, Rebecca L Hannah, Mun Chiang Chan (+5 others)
<span title="2016-02-22">2016</span> <i title="eLife Sciences Publications, Ltd"> <a target="_blank" rel="noopener" href="" style="color: black;">eLife</a> </i> &nbsp;
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
more &raquo; ... s (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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.7554/elife.11469</a> <a target="_blank" rel="external noopener" href="">pmid:26901438</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC4798972</a> <a target="_blank" rel="external noopener" href="">fatcat:kilulyb7u5dcfdwcxvq4k3kfyu</a> </span>
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