An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability
- University Hospital Essen, Germany
- University of Cambridge, United Kingdom
- University of Oxford, United Kingdom
- Walter and Eliza Hall Institute of Medical Research, Australia
- University of Pennsylvania, United States
- VU University Amsterdam, Netherlands
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 leukemogenic TF fusion protein perturbs key HSPC regulators. The approach presented here should help to improve our understanding of both normal physiological and disease processes.
Article and author information
Author details
Reviewing Editor
- Amy J Wagers, Harvard University, United States
Ethics
Animal experimentation: All mice were housed in microisolator cages and provided continuously with sterile food, water, and bedding. All mice were kept in specified pathogen-free conditions, and all procedures were performed according to the United Kingdom Home Office regulations under project licence 70/8406
Version history
- Received: September 9, 2015
- Accepted: February 12, 2016
- Accepted Manuscript published: February 22, 2016 (version 1)
- Version of Record published: March 10, 2016 (version 2)
Copyright
© 2016, Schütte et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability
eLife 5:e11469.
https://doi.org/10.7554/eLife.11469
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