An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability
Open accessAbstract
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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Combinatorial occupancy of chromatin by multiple master transcription factors has revealed regulatory networks important for hematopoiesis.
“For instance, the combinatorial occupancy of chromatin by multiple master TFs has revealed regulatory networks that are important for hematopoiesis (Beck et al., 2013; Schütte et al., 2016), as well as key regulatory elements necessary for HSC self-renewal (Bahr et al., 2018).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Schütte et al., 2016
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- Authors
- Schütte, J., Wang, H., Antoniou, S., Jarratt, A., Wilson, N. K., Riepsaame, J., Calero-Nieto, F. J., Moignard, V., Basilico, S., Kinston, S. J., Hannah, R. L., Chan, M. C., Nürnberg, S. T., Ouwehand, W. H., Bonzanni, N., de Bruijn, M. F., & Göttgens, B.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Oxford (GB)
- Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
- NHS Blood and Transplant (GB)
- The Netherlands Cancer Institute (NL)
- MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
- Corresponding author
- Bonzanni, Nicola
- Göttgens, Berthold
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-02-22
- Volume
- 5
- Pages
- e11469-e11469
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4798972
- OpenAlex
- W2287204676
- Cited by
- 63
- References
- 57
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 3 · 2019: 11 · 2018: 6 · 2017: 14 · 2016: 6
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (100140, G097922, G0900729/1)
- Cancer Research UK (C1163/A12765)
- Leukaemia and Lymphoma Research (12029)
- Biotechnology and Biological Sciences Research Council (BB/I00050X/1)
- National Institute for Health Research
- Medical Research Council (G0900951)
- MRC Molecular Haematology Unit (Oxford) core award
- Weizmann-UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- hematopoietic stem and progenitor cells, transcriptional regulatory networks, regulatory network reconstruction, lineage identity, ChIP-seq, single-cell expression profiling, hematopoiesis
- MeSH terms
- Animals, Cell Line, Computer Simulation, Hematopoiesis, Hematopoietic Stem Cells, Models, Theoretical, Transcription Factors, Sequence Analysis, DNA, Gene Expression Profiling, Chromatin Immunoprecipitation, Mice, Gene Regulatory Networks
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