| Literature DB >> 26901438 |
Judith Schütte1,2, Huange Wang1,2, Stella Antoniou3, Andrew Jarratt3, Nicola K Wilson1,2, Joey Riepsaame3, Fernando J Calero-Nieto1,2, Victoria Moignard1,2, Silvia Basilico1,2, Sarah J Kinston1,2, Rebecca L Hannah1,2, Mun Chiang Chan3, Sylvia T Nürnberg4,5, Willem H Ouwehand4,5, Nicola Bonzanni6,7, Marella Ftr de Bruijn3, Berthold Göttgens1,2.
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.Entities:
Keywords: chromosomes; computational biology; genes; mouse; regulatory network; single cell; stem cells; systems biology
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Year: 2016 PMID： 26901438 PMCID： PMC4798972 DOI： 10.7554/eLife.11469
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.140