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

作者：Schuette Judith; Wang Huange; Antoniou Stella; Jarratt Andrew; Wilson Nicola K; Riepsaame Joey; Calero Nieto Fernando J; Moignard Victoria; Basilico Silvia; Kinston Sarah J; Hannah Rebecca L; Chan Mun Chiang; Nuernberg Sylvia T; Ouwehand Willem H; Bonzanni Nicola^*; de Bruijn Marella F T R^*; Goettgens Berthold

来源：eLife, 2016, 5: e11469.

DOI：10.7554/eLife.11469

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.

• 出版日期2016-2-22
• 单位河北医科大学