Blau, H. M. How fixed is the differentiated state? Lessons from heterokaryons. Trends Genet.5, 268–272 (1989) CASPubMed Google Scholar
Davis, R. L., Weintraub, H. & Lassar, A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell51, 987–1000 (1987) ArticleCASPubMed Google Scholar
Kulessa, H., Frampton, J. & Graf, T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev.9, 1250–1262 (1995)This paper, together with refs 19 and 20, established the principle of transcription factor cross-antagonisms. CASPubMed Google Scholar
Gurdon, J. B. & Byrne, J. A. The first half-century of nuclear transplantation. Proc. Natl Acad. Sci. USA100, 8048–8052 (2003) ADSCASPubMedPubMed Central Google Scholar
Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J. & Campbell, K. H. Viable offspring derived from fetal and adult mammalian cells. Nature385, 810–813 (1997) ADSCASPubMed Google Scholar
Gurdon, J. B. & Melton, D. A. Nuclear reprogramming in cells. Science322, 1811–1815 (2008) ADSCASPubMed Google Scholar
Hochedlinger, K. & Jaenisch, R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature415, 1035–1038 (2002) ADSCASPubMed Google Scholar
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell126, 663–676 (2006) ArticleCASPubMed Google Scholar
Slack, J. M. Metaplasia and transdifferentiation: from pure biology to the clinic. Nature Rev. Mol. Cell Biol.8, 369–378 (2007) CAS Google Scholar
Yang, J. & Weinberg, R. A. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell14, 818–829 (2008) CASPubMed Google Scholar
Kragl, M. et al. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature460, 60–65 (2009) ADSCASPubMed Google Scholar
Chen, M. J., Yokomizo, T., Zeigler, B. M., Dzierzak, E. & Speck, N. A. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature457, 887–891 (2009) ADSCASPubMedPubMed Central Google Scholar
Lancrin, C. et al. The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature457, 892–895 (2009) ADSCASPubMedPubMed Central Google Scholar
Dzierzak, E. & Speck, N. A. Of lineage and legacy: the development of mammalian hematopoietic stem cells. Nature Immunol.9, 129–136 (2008) CAS Google Scholar
Eilken, H. M., Nishikawa, S. & Schroeder, T. Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature457, 896–900 (2009)An example of ‘transdifferentiation’ in the context of normal lineage progression; also highlights how real-time visualization may show cell fate conversions that are otherwise hard to document. ADSCASPubMed Google Scholar
Zhou, Q. & Melton, D. A. Extreme makeover: converting one cell into another. Cell Stem Cell3, 382–388 (2008) CASPubMed Google Scholar
Visvader, J. E., Elefanty, A. G., Strasser, A. & Adams, J. M. GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. EMBO J.11, 4557–4564 (1992) CASPubMedPubMed Central Google Scholar
Nerlov, C. & Graf, T. PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev.12, 2403–2412 (1998) CASPubMedPubMed Central Google Scholar
Heyworth, C., Pearson, S., May, G. & Enver, T. Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. EMBO J.21, 3770–3781 (2002) CASPubMedPubMed Central Google Scholar
Zhang, P. et al. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity21, 853–863 (2004) CASPubMed Google Scholar
Xie, H., Ye, M., Feng, R. & Graf, T. Stepwise reprogramming of B cells into macrophages. Cell117, 663–676 (2004) CASPubMed Google Scholar
Laiosa, C. V., Stadtfeld, M., Xie, H., de Andres-Aguayo, L. & Graf, T. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBPα and PU.1 transcription factors. Immunity25, 731–744 (2006) CASPubMed Google Scholar
Arinobu, Y. et al. Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages. Cell Stem Cell1, 416–427 (2007) CASPubMed Google Scholar
Iwasaki, H. & Akashi, K. Myeloid lineage commitment from the hematopoietic stem cell. Immunity26, 726–740 (2007) CASPubMed Google Scholar
Okuno, Y. et al. Potential autoregulation of transcription factor PU.1 by an upstream regulatory element. Mol. Cell. Biol.25, 2832–2845 (2005) CASPubMedPubMed Central Google Scholar
Yu, C. et al. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo . J. Exp. Med.195, 1387–1395 (2002) CASPubMedPubMed Central Google Scholar
Ptashne, M. A Genetic Switch. Phage Lambda Revisited 3rd edn (Cold Spring Harbor Laboratory Press, 2004) Google Scholar
Cantor, A. B. & Orkin, S. H. Hematopoietic development: a balancing act. Curr. Opin. Genet. Dev.11, 513–519 (2001) CASPubMed Google Scholar
Graf, T. Differentiation plasticity of hematopoietic cells. Blood99, 3089–3101 (2002) CASPubMed Google Scholar
Zhang, P. et al. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc. Natl Acad. Sci. USA96, 8705–8710 (1999) ADSCASPubMedPubMed Central Google Scholar
Stopka, T., Amanatullah, D. F., Papetti, M. & Skoultchi, A. I. PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure. EMBO J.24, 3712–3723 (2005) CASPubMedPubMed Central Google Scholar
Rhodes, J. et al. Interplay of Pu.1 and Gata1 determines myelo-erythroid progenitor cell fate in zebrafish. Dev. Cell8, 97–108 (2005) In vivoevidence for the importance of GATA1:PU.1 interplay in lineage specification. CASPubMed Google Scholar
Galloway, J. L., Wingert, R. A., Thisse, C., Thisse, B. & Zon, L. I. Loss of Gata1 but not Gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos. Dev. Cell8, 109–116 (2005) CASPubMed Google Scholar
Warga, R. M., Kane, D. A. & Ho, R. K. Fate mapping embryonic blood in zebrafish: multi- and unipotential lineages are segregated at gastrulation. Dev. Cell16, 744–755 (2009) CASPubMedPubMed Central Google Scholar
Nutt, S. L., Heavey, B., Rolink, A. G. & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature401, 556–562 (1999) ADSCASPubMed Google Scholar
Cobaleda, C., Jochum, W. & Busslinger, M. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature449, 473–477 (2007) ADSCASPubMed Google Scholar
Rothenberg, E. V. Cell lineage regulators in B and T cell development. Nature Immunol.8, 441–444 (2007) CAS Google Scholar
Davidson, E. H. & Levine, M. S. Properties of developmental gene regulatory networks. Proc. Natl Acad. Sci. USA105, 20063–20066 (2008) ADSCASPubMedPubMed Central Google Scholar
Zhou, L. et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature453, 236–240 (2008) ADSCASPubMedPubMed Central Google Scholar
Rieger, M. A., Hoppe, P. S., Smejkal, B. M., Eitelhuber, A. C. & Schroeder, T. Hematopoietic cytokines can instruct lineage choice. Science325, 217–218 (2009) ADSCASPubMed Google Scholar
Sarrazin, S. et al. MafB restricts M-CSF-dependent myeloid commitment divisions of hematopoietic stem cells. Cell138, 300–313 (2009)An example of how extrinsic signals may act through intrinsic regulators to specify lineage fates; ref. 57 addresses a similar issue from a mathematical modelling perspective. CASPubMed Google Scholar
Smith, J., Wardle, F., Loose, M., Stanley, E. & Patient, R. Germ layer induction in ESC–following the vertebrate roadmap. Curr. Protocols Stem Cell Biol.1, 1D.1.1–1D.1.22 (2007) Google Scholar
Iwasaki, H. et al. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev.20, 3010–3021 (2006)Showed that the order of transcription factor expression can induce different cell fates. CASPubMedPubMed Central Google Scholar
Sieweke, M. H. & Graf, T. A transcription factor party during blood cell differentiation. Curr. Opin. Genet. Dev.8, 545–551 (1998) CASPubMed Google Scholar
Waddington, C. H. The Strategy of the Genes (Allen & Unwin, 1957) Google Scholar
Kauffman, S. Metabolic stability and epigenesis in randomly constructed genetic nets. J. Theor. Biol.22, 437–467 (1969) MathSciNetCASPubMed Google Scholar
Kauffman, S. Origins of Order: Self-organization and Selection in Evolution (Oxford Univ. Press, 1993) Google Scholar
Enver, T., Pera, M., Peterson, C. & Andrews, P. W. Stem cell states, fates, and the rules of attraction. Cell Stem Cell4, 387–397 (2009) CASPubMed Google Scholar
Hu, M. et al. Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev.11, 774–785 (1997) CASPubMed Google Scholar
Miyamoto, T. et al. Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev. Cell3, 137–147 (2002) CASPubMed Google Scholar
Månsson, R. et al. Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity26, 407–419 (2007) PubMed Google Scholar
Enver, T., Heyworth, C. M. & Dexter, T. M. Do stem cells play dice? Blood92, 348–351,–352 (1998) CASPubMed Google Scholar
Graf, T. & Stadtfeld, M. Heterogeneity of embryonic and adult stem cells. Cell Stem Cell3, 480–483 (2008) CASPubMed Google Scholar
Chambers, I. et al. Nanog safeguards pluripotency and mediates germline development. Nature450, 1230–1234 (2007) ADSCASPubMed Google Scholar
Chickarmane, V., Enver, T. & Peterson, C. Computational modeling of the hematopoietic erythroid-myeloid switch reveals insights into cooperativity, priming, and irreversibility. PLoS Comput. Biol.5, e1000268 (2009) ADSPubMedPubMed Central Google Scholar
Huang, S., Guo, Y. P., May, G. & Enver, T. Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev. Biol.305, 695–713 (2007)Refs 57, 58 and 59 highlight how mathematical modelling of cross-antagonistic circuits illuminates their dynamic behaviour and capacity to effect stable lineage choice decisions. CASPubMed Google Scholar
Roeder, I. & Glauche, I. Towards an understanding of lineage specification in hematopoietic stem cells: a mathematical model for the interaction of transcription factors GATA-1 and PU.1. J. Theor. Biol.241, 852–865 (2006) MathSciNetCASPubMed Google Scholar
Swiers, G., Patient, R. & Loose, M. Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification. Dev. Biol.294, 525–540 (2006) CASPubMed Google Scholar
Laslo, P. et al. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell126, 755–766 (2006)An example of sequential cross-antagonistic switches in the specification of cell lineage. CASPubMed Google Scholar
Hwang, E. S., Szabo, S. J., Schwartzberg, P. L. & Glimcher, L. H. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science307, 430–433 (2005) ADSCASPubMed Google Scholar
Yechoor, V. et al. Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Dev. Cell16, 358–373 (2009) CASPubMedPubMed Central Google Scholar
Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J. & Melton, D. A. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature455, 627–632 (2008)Showed that expression in the pancreas of a combination of three key regulators re-specifies one somatic cell type into another functional cell type,in vivo. ADSCASPubMedPubMed Central Google Scholar
Starck, J. et al. Functional cross-antagonism between transcription factors FLI-1 and EKLF. Mol. Cell. Biol.23, 1390–1402 (2003) CASPubMedPubMed Central Google Scholar
Querfurth, E. et al. Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors. Genes Dev.14, 2515–2525 (2000) CASPubMedPubMed Central Google Scholar
Kajimura, S. et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev.22, 1397–1409 (2008) CASPubMedPubMed Central Google Scholar
Heins, N. et al. Glial cells generate neurons: the role of the transcription factor Pax6. Nature Neurosci.5, 308–315 (2002) CASPubMed Google Scholar
Jessberger, S., Toni, N., Clemenson, G. D., Ray, J. & Gage, F. H. Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nature Neurosci.11, 888–893 (2008) CASPubMed Google Scholar
Gubbels, S. P., Woessner, D. W., Mitchell, J. C., Ricci, A. J. & Brigande, J. V. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature455, 537–541 (2008) ADSCASPubMedPubMed Central Google Scholar
Horb, M. E., Shen, C. N., Tosh, D. & Slack, J. M. Experimental conversion of liver to pancreas. Curr. Biol.13, 105–115 (2003) CASPubMed Google Scholar
Niwa, H. et al. Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell123, 917–929 (2005) CASPubMed Google Scholar
Ralston, A. & Rossant, J. Genetic regulation of stem cell origins in the mouse embryo. Clin. Genet.68, 106–112 (2005) CASPubMed Google Scholar
Aoi, T. et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science321, 699–702 (2008) ADSCASPubMed Google Scholar
Stadtfeld, M., Brennand, K. & Hochedlinger, K. Reprogramming of pancreatic β cells into induced pluripotent stem cells. Curr. Biol.18, 890–894 (2008) CASPubMedPubMed Central Google Scholar
Yamanaka, S. Elite and stochastic models for induced pluripotent stem cell generation. Nature460, 49–52 (2009) ADSCASPubMed Google Scholar
Kim, J. B. et al. Oct4-induced pluripotency in adult neural stem cells. Cell136, 411–419 (2009) CASPubMed Google Scholar
Loh, Y. H., Zhang, W., Chen, X., George, J. & Ng, H. H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev.21, 2545–2557 (2007) CASPubMedPubMed Central Google Scholar
Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell125, 315–326 (2006) CASPubMed Google Scholar
Alon, U. An Introduction to Systems Biology. Design Principles of Biological Circuits (Chapman and Hall/CRC, 2006) MATH Google Scholar
Chickarmane, V., Troein, C., Nuber, U. A., Sauro, H. M. & Peterson, C. Transcriptional dynamics of the embryonic stem cell switch. PLoS Comput. Biol.2, e123 (2006) ADSPubMedPubMed Central Google Scholar
Chickarmane, V. & Peterson, C. A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. PLoS One3, e3478 (2008) ADSPubMedPubMed Central Google Scholar
Chang, H. H., Hemberg, M., Barahona, M., Ingber, D. E. & Huang, S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature453, 544–547 (2008) ADSCASPubMedPubMed Central Google Scholar
Boukamp, P., Chen, J., Gonzales, F., Jones, P. A. & Fusenig, N. E. Progressive stages of “transdifferentiation” from epidermal to mesenchymal phenotype induced by MyoD1 transfection, 5-aza-2′-deoxycytidine treatment, and selection for reduced cell attachment in the human keratinocyte line HaCaT. J. Cell Biol.116, 1257–1271 (1992) CASPubMed Google Scholar
Feng, R. et al. PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells. Proc. Natl Acad. Sci. USA105, 6057–6062 (2008) ADSCASPubMedPubMed Central Google Scholar
Palermo, A. et al. Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional. FASEB J.23, 1431–1440 (2009) CASPubMedPubMed Central Google Scholar
Singh, H., Medina, K. L. & Pongubala, J. M. Contingent gene regulatory networks and B cell fate specification. Proc. Natl Acad. Sci. USA102, 4949–4953 (2005) ADSCASPubMedPubMed Central Google Scholar
Kitajima, K., Zheng, J., Yen, H., Sugiyama, D. & Nakano, T. Multipotential differentiation ability of GATA-1-null erythroid-committed cells. Genes Dev.20, 654–659 (2006) CASPubMedPubMed Central Google Scholar
Judson, R. L., Babiarz, J. E., Venere, M. & Blelloch, R. Embryonic stem cell-specific microRNAs promote induced pluripotency. Nature Biotechnol.27, 459–461 (2009) CAS Google Scholar
Takeuchi, J. K. & Bruneau, B. G. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature459, 708–711 (2009) ADSCASPubMedPubMed Central Google Scholar
Viswanathan, S. R., Daley, G. Q. & Gregory, R. I. Selective blockade of microRNA processing by Lin28. Science320, 97–100 (2008) ADSCASPubMedPubMed Central Google Scholar
Feng, B., Ng, J. H., Heng, J. C. & Ng, H. H. Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell4, 301–312 (2009) CASPubMed Google Scholar
Collombat, P. et al. Opposing actions of Arx4 and Pax4 in endocrine pancreas development. Genes Dev.15, 2591–2603 (2003) Google Scholar
Lagha, M. et al. Pax3/7:Foxc2 reciprocal repression in the somite modulates multipotent cell fates. Dev. Cell (in the press)