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="https://fatcat.wiki/container/en4qj5ijrbf5djxx7p5zzpjyoq" 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="https://doi.org/10.7554/elife.11469">doi:10.7554/elife.11469</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/26901438">pmid:26901438</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC4798972/">pmcid:PMC4798972</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/kilulyb7u5dcfdwcxvq4k3kfyu">fatcat:kilulyb7u5dcfdwcxvq4k3kfyu</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170921202037/https://cdn.elifesciences.org/articles/11469/elife-11469-v1.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/a0/0a/a00ae501f1222fc064d06b01615c8df40824f595.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.7554/elife.11469"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> elifesciences.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798972" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>