An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability
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 repo...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/11469 |
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doaj-1de7a5bf09f74bf7bca63a4f8f5adab5 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 Sylvia T Nürnberg Willem H Ouwehand Nicola Bonzanni Marella FTR de Bruijn Berthold Göttgens |
| spellingShingle |
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 Sylvia T Nürnberg Willem H Ouwehand Nicola Bonzanni Marella FTR de Bruijn Berthold Göttgens An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability eLife regulatory network single cell stem cells |
| author_facet |
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 Sylvia T Nürnberg Willem H Ouwehand Nicola Bonzanni Marella FTR de Bruijn Berthold Göttgens |
| author_sort |
Judith Schütte |
| title |
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| title_short |
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| title_full |
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| title_fullStr |
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| title_full_unstemmed |
An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| title_sort |
experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2016-02-01 |
| description |
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. |
| topic |
regulatory network single cell stem cells |
| url |
https://elifesciences.org/articles/11469 |
| work_keys_str_mv |
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doaj-1de7a5bf09f74bf7bca63a4f8f5adab52021-05-05T00:16:36ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.11469An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stabilityJudith Schütte0Huange Wang1Stella Antoniou2Andrew Jarratt3Nicola K Wilson4Joey Riepsaame5Fernando J Calero-Nieto6Victoria Moignard7Silvia Basilico8Sarah J Kinston9Rebecca L Hannah10Mun Chiang Chan11Sylvia T Nürnberg12Willem H Ouwehand13Nicola Bonzanni14Marella FTR de Bruijn15Berthold Göttgens16https://orcid.org/0000-0001-6302-5705Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom; NHS Blood and Transplant, Cambridge, United KingdomDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom; NHS Blood and Transplant, Cambridge, United KingdomIBIVU Centre for Integrative Bioinformatics, VU University Amsterdam, Amsterdam, Netherlands; Netherlands Cancer Institute, Amsterdam, NetherlandsMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomTranscription 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.https://elifesciences.org/articles/11469regulatory networksingle cellstem cells |