학술논문
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability.
Document Type
Article
Author
Schütte, Judith; Huange Wang; Antoniou, Stella; Jarratt, Andrew; Wilson, Nicola K.; Riepsaame, Joey; Calero-Nieto, Fernando J.; Moignard, Victoria; Basilico, Silvia; Kinston, Sarah J.; Hannah, Rebecca L.; Mun Chiang Chan; Nürnberg, Sylvia T.; Ouwehand, Willem H.; Bonzanni, Nicola; de Bruijn, Marella F. T. R.; Göttgens, Berthold
Source
Subject
*HEMATOPOIETIC growth factors
*TRANSCRIPTION factors
*TRANS-regulatory elements (Genetics)
*CELL culture
*CELL sheets (Biology)
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Language
ISSN
2050-084X
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. [ABSTRACT FROM AUTHOR]