An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability

eLife

Volumn 5, Issue FEBRUARY2016, 2016, Pages

  Schütte, Judith ^a,b,g   Wang, Huange ^a,b   Antoniou, Stella ^c   Jarratt, Andrew ^c,h   Wilson, Nicola K ^a,b   Riepsaame, Joey ^c   Calero Nieto, Fernando J ^a,b   Moignard, Victoria ^a,b   Basilico, Silvia ^a,b   Kinston, Sarah J ^a,b   Hannah, Rebecca L ^a,b   Chan, Mun Chiang ^c   Nürnberg, Sylvia T ^b,d,i   Ouwehand, Willem H ^b,d   Bonzanni, Nicola ^e,f   De Bruijn, Marella F T R ^c   Gӧttgens, Berthold ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d NHS BLOOD AND TRANSPLANT   (United Kingdom)

^e VU UNIVERSITY AMSTERDAM   (Netherlands)

^f NETHERLANDS CANCER INSTITUTE   (Netherlands)

^g UNIVERSITY HOSPITAL ESSEN   (Germany)

^h WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

ⁱ UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CIS ACTING ELEMENT; HISTONE H3; HYBRID PROTEIN; ONCOPROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR FLI1; TRANSCRIPTION FACTOR GATA 2; TRANSCRIPTION FACTOR GFI1B; TRANSCRIPTION FACTOR LYL1; TRANSCRIPTION FACTOR MEIS1; TRANSCRIPTION FACTOR PU 1; TRANSCRIPTION FACTOR RUNX1; TRANSCRIPTION FACTOR TAL1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; E BOX ELEMENT; EMBRYO; ENHANCER REGION; GENE EXPRESSION; GENE OVEREXPRESSION; GENE REGULATORY NETWORK; GENE SILENCING; HEMATOPOIETIC STEM CELL; HISTONE ACETYLATION; LUCIFERASE ASSAY; MOUSE; MUTAGENESIS; NONHUMAN; NUCLEOTIDE SEQUENCE; POLYMERASE CHAIN REACTION; PROTEIN DNA INTERACTION; PROTEIN EXPRESSION; REPORTER GENE; SIMULATION; TRANSGENIC MOUSE; TRANSIENT EXPRESSION; TRANSIENT TRANSFECTION; ANIMAL; CELL LINE; COMPUTER SIMULATION; DNA SEQUENCE; GENE EXPRESSION PROFILING; HEMATOPOIESIS; METABOLISM; PHYSIOLOGY; THEORETICAL MODEL; VALIDATION STUDY;

ANIMALS; CELL LINE; CHROMATIN IMMUNOPRECIPITATION; COMPUTER SIMULATION; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORKS; HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; MICE; MODELS, THEORETICAL; SEQUENCE ANALYSIS, DNA; TRANSCRIPTION FACTORS;

EID: 84961262349     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.11469     Document Type: Article

References (57)

1. Batta K, Florkowska M, Kouskoff V, Lacaud G. 2014. Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells. Cell Reports 9:1871-1884. doi: 10.1016/j.celrep.2014.11.002
2. Beck D, Thoms JAI, Perera D, Schutte J, Unnikrishnan A, Knezevic K, Kinston SJ, Wilson NK, O’Brien TA, Gottgens B, Wong JWH, Pimanda JE. 2013. Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes. Blood 122:e12-e22. doi: 10.1182/blood-2013-03-490425
3. Bee T, Ashley ELK, Bickley SRB, Jarratt A, Li P-S, Sloane-Stanley J, Gottgens B, de Bruijn MFTR. 2009. The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters. Blood 113:5121-5124. doi: 10.1182/blood-2008-12-193003
4. Bee T, Swiers G, Muroi S, Pozner A, Nottingham W, Santos AC, Li PS, Taniuchi I, de Bruijn MFTR. 2010. Nonredundant roles for Runx1 alternative promoters reflect their activity at discrete stages of developmental hematopoiesis. Blood 115:3042-3050. doi: 10.1182/blood-2009-08-238626
5. Bonzanni N, Garg A, Feenstra KA, Schutte J, Kinston S, Miranda-Saavedra D, Heringa J, Xenarios I, Gottgens B. 2013. Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model. Bioinformatics 29:i80-i88. doi: 10.1093/bioinformatics/btt243
6. Busch K, Klapproth K, Barile M, Flossdorf M, Holland-Letz T, Schlenner SM, Reth M, Hofer T, Rodewald H-R. 2015. Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature 518:542-546. doi: 10.1038/nature14242
7. Calero-Nieto FJ, Ng FS, Wilson NK, Hannah R, Moignard V, Leal-Cervantes AI, Jimenez-Madrid I, Diamanti E, Wernisch L, Gottgens B. 2014. Key regulators control distinct transcriptional programmes in blood progenitor and mast cells. The EMBO Journal 33:1212-1226. doi: 10.1002/embj.201386825
8. Capron C, Lécluse Y, Kaushik AL, Foudi A, Lacout C, Sekkai D, Godin I, Albagli O, Poullion I, Svinartchouk F, Schanze E, Vainchenker W, Sablitzky F, Bennaceur-Griscelli A, Duménil D. 2006. The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and b-cell differentiation. Blood 107:4678-4686. doi: 10.1182/blood-2005-08-3145
9. Chan WYI, Follows GA, Lacaud G, Pimanda JE, Landry J-R, Kinston S, Knezevic K, Piltz S, Donaldson IJ, Gambardella L, Sablitzky F, Green AR, Kouskoff V, Gottgens B. 2007. The paralogous hematopoietic regulators Lyl1 and scl are coregulated by ets and GATA factors, but Lyl1 cannot rescue the early sclphenotype. Blood 109:1908-1916. doi: 10.1182/blood-2006-05-023226
10. Davidson EH. 2009. Network design principles from the sea urchin embryo. Current Opinion in Genetics & Development 19:535-540. doi: 10.1016/j.gde.2009.10.007
11. Davidson EH. 2010. Emerging properties of animal gene regulatory networks. Nature 468:911-920. doi: 10.1038/nature09645
12. Dexter TM, Allen TD, Scott D, Teich NM. 1979. Isolation and characterisation of a bipotential haematopoietic cell line. Nature 277:471-474. doi: 10.1038/277471a0
13. Dunn S-J, Martello G, Yordanov B, Emmott S, Smith AG. 2014. Defining an essential transcription factor program for naive pluripotency. Science 344:1156-1160. doi: 10.1126/science.1248882
14. Gazit R, Garrison BS, Rao TN, Shay T, Costello J, Ericson J, Kim F, Collins JJ, Regev A, Wagers AJ, Rossi DJ. 2013 Immunological Genome Project ConsortiumImmunological Genome Project Consortium. Transcriptome analysis identifies regulators of hematopoietic stem and progenitor cells. Stem Cell Reports 1:266-280. doi: 10.1016/j.stemcr.2013.07.004
15. Gottgens B, Broccardo C, Sanchez M-J, Deveaux S, Murphy G, Gothert JR, Kotsopoulou E, Kinston S, Delaney L, Piltz S, Barton LM, Knezevic K, Erber WN, Begley CG, Frampton J, Green AR. 2004. The scl +18/19 stem cell enhancer is not required for hematopoiesis: identification of a 5’ bifunctional hematopoietic-endothelial enhancer bound by fli-1 and elf-1. Molecular and Cellular Biology 24:1870-1883. doi: 10.1128/MCB.24.5.1870-1883.2004
16. Gottgens B, Ferreira R, Sanchez M-J, Ishibashi S, Li J, Spensberger D, Lefevre P, Ottersbach K, Chapman M, Kinston S, Knezevic K, Hoogenkamp M, Follows GA, Bonifer C, Amaya E, Green AR. 2010. Cis-regulatory remodeling of the SCL locus during vertebrate evolution. Molecular and Cellular Bioogy 30:5741-5751. doi: 10.1128/MCB.00870-10
17. Gottgens B. 2015. Regulatory network control of blood stem cells. Blood 125:2614-2620. doi: 10.1182/blood-2014-08-570226
18. Graf T, Enver T. 2009. Forcing cells to change lineages. Nature 462:587-594. doi: 10.1038/nature08533
19. Gottgens B, Nastos A, Kinston S, Piltz S, Delabesse EC, Stanley M, Sanchez MJ, Ciau-Uitz A, Patient R, Green AR. 2002. Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing ets and GATA factors. The EMBO Journal 21:3039-3050. doi: 10.1093/emboj/cdf286
20. Hall MA, Curtis DJ, Metcalf D, Elefanty AG, Sourris K, Robb L, Gothert JR, Jane SM, Begley CG. 2003. The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12. Proceedings of the National Academy of Sciences of the United States of America 100:992-997. doi: 10.1073/pnas.0237324100
21. Hardison RC, Taylor J. 2012. Genomic approaches towards finding cis-regulatory modules in animals. Nature Reviews Genetics 13:469-483. doi: 10.1038/nrg3242
22. Jojic V, Shay T, Sylvia K, Zuk O, Sun X, Kang J, Regev A, Koller D, Best AJ, Knell J, Goldrath A, Joic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemarte-Pelletier A, Malhotra D, Turley S. 2013 Immunological Genome Project ConsortiumImmunological Genome Project Consortium Identification of transcriptional regulators in the mouse immune system. Nature Immunology 14:633-643. doi: 10.1038/ni.2587
23. Koller D, Friedman N. 2009. Probabilistic Graphical Models Principles and Techniques. MIT Press.
24. Krumsiek J, Marr C, Schroeder T, Theis FJ. 2011. Hierarchical differentiation of myeloid progenitors is encoded in the transcription factor network. PLoS ONE 6:e22649. doi: 10.1371/journal.pone.0022649
25. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with bowtie 2. Nature Methods 9:357-359. doi: 10.1038/nmeth.1923
26. Lelieveld SH, Schutte J, Dijkstra MJJ, Bawono P, Kinston SJ, Gottgens B, Heringa J, Bonzanni N. 2015. ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites. Nucleic Acids Research:gkv 1518. doi: 10.1093/nar/gkv1518
27. Licht JD. 2001. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML. Oncogene 20:5660-5679. doi: 10.1038/sj.onc.1204593
28. Longabaugh WJR, Davidson EH, Bolouri H. 2005. Computational representation of developmental genetic regulatory networks. Developmental Biology 283:1-16. doi: 10.1016/j.ydbio.2005.04.023
29. Mikkola HKA, Klintman J, Yang H, Hock H, Schlaeger TM, Fujiwara Y, Orkin SH. 2003. Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene. Nature 421:547-551. doi: 10.1038/nature01345
30. Moignard V, Macaulay IC, Swiers G, Buettner F, Schutte J, Calero-Nieto FJ, Kinston S, Joshi A, Hannah R, Theis FJ, Jacobsen SE, de Bruijn MF, Gottgens B. 2013. Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis. Nature Cell Biology 15:363-372. doi: 10.1038/ncb2709
31. Narula J, Smith AM, Gottgens B, Igoshin OA. 2010. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate. PLoS Computational Biology 6:e1000771. doi: 10.1371/journal.pcbi.1000771
32. Narula J, Williams CJ, Tiwari A, Marks-Bluth J, Pimanda JE, Igoshin OA. 2013. Mathematical model of a gene regulatory network reconciles effects of genetic perturbations on hematopoietic stem cell emergence. Developmental Biology 379:258-269. doi: 10.1016/j.ydbio.2013.04.016
33. Nottingham WT, Jarratt A, Burgess M, Speck CL, Cheng J-F, Prabhakar S, Rubin EM, Li P-S, Sloane-Stanley J, Kong-a-San J, de Bruijn MFTR. 2007. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood 110:4188-4197. doi: 10.1182/blood-2007-07-100883
34. Peter IS, Davidson EH. 2011. A gene regulatory network controlling the embryonic specification of endoderm. Nature 474:635-639. doi: 10.1038/nature10100
35. Petricka JJ, Benfey PN. 2011. Reconstructing regulatory network transitions. Trends in Cell Biology 21:442-451. doi: 10.1016/j.tcb.2011.05.001
36. Pimanda JE, Gottgens B. 2010. Gene regulatory networks governing haematopoietic stem cell development and identity. The International Journal of Developmental Biology 54:1201-1211. doi: 10.1387/ijdb.093038jp
37. Pimanda JE, Ottersbach K, Knezevic K, Kinston S, Chan WYI, Wilson NK, Landry J-R, Wood AD, Kolb-Kokocinski A, Green AR, Tannahill D, Lacaud G, Kouskoff V, Gottgens B. 2007. Gata2, Fli1, and scl form a recursively wired gene-regulatory circuit during early hematopoietic development. Proceedings of the National Academy of Sciences of the United States of America 104:17692-17697. doi: 10.1073/pnas.0707045104
38. Pinto do O P, Kolterud A, Carlsson L. 1998. Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors. The EMBO Journal 17:5744-5756. doi: 10.1093/emboj/17.19.5744
39. Riddell J, Gazit R, Garrison BS, Guo G, Saadatpour A, Mandal PK, Ebina W, Volchkov P, Yuan G-C, Orkin SH, Rossi DJ. 2014. Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell 157:549-564. doi: 10.1016/j.cell.2014.04.006
40. Sanchez-Castillo M, Ruau D, Wilkinson AC, Ng FSL, Hannah R, Diamanti E, Lombard P, Wilson NK, Gottgens B. 2015. CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities. Nucleic Acids Research 43:D1117-D1123. doi: 10.1093/nar/gku895
41. Schutte J, Moignard V, Gottgens B. 2012. Establishing the stem cell state: insights from regulatory network analysis of blood stem cell development. Wiley Interdisciplinary Reviews. Systems Biology and Medicine 4:285-295. doi: 10.1002/wsbm.1163
42. Shivdasani RA, Mayer EL, Orkin SH. 1995. Absence of blood formation in mice lacking the t-cell leukaemia oncoprotein tal-1/SCL. Nature 373:432-434. doi: 10.1038/373432a0
43. Sinclair AM, Gottgens B, Barton LM, Stanley ML, Pardanaud L, Klaine M, Gering M, Bahn S, Sanchez M-J, Bench AJ, Fordham JL, Bockamp E-O, Green AR. 1999. Distinct 5¢ SCL enhancers direct transcription to developing brain, spinal cord, and endothelium: neural expression is mediated by GATA factor binding sites. Developmental Biology 209:128-142. doi: 10.1006/dbio.1999.9236
44. Souroullas GP, Salmon JM, Sablitzky F, Curtis DJ, Goodell MA. 2009. Adult hematopoietic stem and progenitor cells require either Lyl1 or scl for survival. Cell Stem Cell 4:180-186. doi: 10.1016/j.stem.2009.01.001
45. Sánchez M, Gottgens B, Sinclair AM, Stanley M, Begley CG, Hunter S, Green AR. 1999. An SCL 3’ enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors. Development 126:3891-3904.
46. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676. doi: 10.1016/j.cell.2006.07.024
47. Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae S-C, Komori T, Ito Y, Littman DR. 2002b. Differential requirements for runx proteins in CD4 repression and epigenetic silencing during t lymphocyte development. Cell 111:621-633. doi: 10.1016/S0092-8674(02)01111-X
48. Taniuchi I, Sunshine MJ, Festenstein R, Littman DR. 2002a. Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Molecular Cell 10:1083-1096. doi: 10.1016/S1097-2765(02)00735-9
49. Tijssen MR, Cvejic A, Joshi A, Hannah RL, Ferreira R, Forrai A, Bellissimo DC, Oram SH, Smethurst PA, Wilson NK, Wang X, Ottersbach K, Stemple DL, Green AR, Ouwehand WH, Gottgens B. 2011. Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Developmental Cell 20:597-609. doi: 10.1016/j.devcel.2011.04.008
50. Wang W, Yang J, Liu H, Lu D, Chen X, Zenonos Z, Campos LS, Rad R, Guo G, Zhang S, Bradley A, Liu P. 2011. Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1. Proceedings of the National Academy of Sciences of the United States of America 108:18283-18288. doi: 10.1073/pnas.1100893108
51. Wilkinson AC, Kawata VKS, Schutte J, Gao X, Antoniou S, Baumann C, Woodhouse S, Hannah R, Tanaka Y, Swiers G, Moignard V, Fisher J, Hidetoshi S, Tijssen MR, de Bruijn MFTR, Liu P, Gottgens B. 2014. Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification. Development 141:4018-4030. doi: 10.1242/dev.115709
52. Wilson NK, Foster SD, Wang X, Knezevic K, Schutte J, Kaimakis P, Chilarska PM, Kinston S, Ouwehand WH, Dzierzak E, Pimanda JE, de Bruijn MFTR, Gottgens B. 2010. Combinatorial transcriptional control in blood Stem/Progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 7:532-544. doi: 10.1016/j.stem.2010.07.016
53. Wilson NK, Miranda-Saavedra D, Kinston S, Bonadies N, Foster SD, Calero-Nieto F, Dawson MA, Donaldson IJ, Dumon S, Frampton J, Janky R, Sun X-H, Teichmann SA, Bannister AJ, Gottgens B. 2009. The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development. Blood 113:5456-5465. doi: 10.1182/blood-2009-01-200048
54. Wozniak RJ, Boyer ME, Grass JA, Lee Y, Bresnick EH. 2007. Context-dependent GATA factor function: combinatorial requirements for transcriptional control in hematopoietic and endothelial cells. Journal of Biological Chemistry 282:14665-14674. doi: 10.1074/jbc.M700792200
55. Xu W, Kee BL. 2007. Growth factor independent 1B (gfi1b) is an E2A target gene that modulates Gata3 in t-cell lymphomas. Blood 109:4406-4414. doi: 10.1182/blood-2006-08-043331
56. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nussbaum C, Myers RM, Brown M, Li W, Liu XS. 2008. Model-based analysis of ChIP-seq (mACS). Genome Biology 9:R137. doi: 10.1186/gb-2008-9-9-r137
57. Zhou Q, Chipperfield H, Melton DA, Wong WH. 2007. A gene regulatory network in mouse embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 104:16438-16443. doi:10.1073/pnas.0701014104