期刊
ELIFE
卷 5, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.11469
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资金
- Wellcome Trust [100140, G097922, G0900729/1]
- Cancer Research UK [C1163/A12765]
- Leukaemia and Lymphoma Research [12029]
- Biotechnology and Biological Sciences Research Council [BB/100050X/1]
- National Institute for Health Research
- Medical Research Council [G0900951]
- MRC Molecular Haematology Unit (Oxford) core award
- Weizmann-UK
- Biotechnology and Biological Sciences Research Council [BB/I00050X/1] Funding Source: researchfish
- British Heart Foundation [RG/09/012/28096] Funding Source: researchfish
- Cancer Research UK [12765] Funding Source: researchfish
- Medical Research Council [MR/M008975/1, MC_PC_12009, G1000801h, G0900951, MC_UU_12009/2, MC_U137970202] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10151, NF-SI-0510-10214, RP-PG-0310-1002] Funding Source: researchfish
- BBSRC [BB/I00050X/1] Funding Source: UKRI
- MRC [MC_U137970202, G0900951, MR/M008975/1, MC_UU_12009/2] Funding Source: UKRI
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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