An Experimentally Validated Network of Nine Haematopoietic Transcription Factors Reveals Mechanisms of Cell State Stability

Overview

Journal Elife

Specialty Biology

Date 2016 Feb 23

PMID 26901438

Citations 36

Authors

Judith Schutte

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

Sylvia T Nurnberg

Willem H Ouwehand

Nicola Bonzanni

Marella Ftr de Bruijn

Berthold Gottgens

Affiliations

Soon will be listed here.

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.

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