Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal (original) (raw)

• Reik, W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447, 425–432 (2007).
  CAS PubMed Google Scholar
• Sasaki, H. & Matsui, Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nature Rev. Genet. 9, 129–140 (2008).
  CAS PubMed Google Scholar
• Dean, W., Santos, F. & Reik, W. Epigenetic reprogramming in early mammalian development and following somatic nuclear transfer. Semin. Cell Dev. Biol. 14, 93–100 (2003).
  CAS PubMed Google Scholar
• Surani, M. A., Hayashi, K. & Hajkova, P. Genetic and epigenetic regulators of pluripotency. Cell 128, 747–762 (2007).
  CAS PubMed Google Scholar
• Oswald, J. et al. Active demethylation of the paternal genome in the mouse zygote. Curr. Biol. 10, 475–478 (2000).
  CAS PubMed Google Scholar
• Mayer, W., Niveleau, A., Walter, J., Fundele, R. & Haaf, T. Demethylation of the zygotic paternal genome. Nature 403, 501–502 (2000).
  CAS PubMed Google Scholar
• Santos, F., Hendrich, B., Reik, W. & Dean, W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev. Biol. 241, 172–182 (2002). A detailed analysis of the DNA methylation dynamics in pre-implantation mouse development.
  CAS PubMed Google Scholar
• Howell, C. Y. et al. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104, 829–838 (2001).
  CAS PubMed Google Scholar
• Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008).
  CAS PubMed PubMed Central Google Scholar
• Vincent, S. D. et al. The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development 132, 1315–1325 (2005).
  CAS PubMed Google Scholar
• Hayashi, K., de Sousa Lopes, S. M. & Surani, M. A. Germ cell specification in mice. Science 316, 394–396 (2007).
  CAS PubMed Google Scholar
• Saitou, M., Barton, S. C. & Surani, M. A. A molecular programme for the specification of germ cell fate in mice. Nature 418, 293–300 (2002).
  CAS PubMed Google Scholar
• Yamazaki, Y. et al. Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc. Natl Acad. Sci. USA 100, 12207–12212 (2003).
  CAS PubMed PubMed Central Google Scholar
• Lee, J. et al. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129, 1807–1817 (2002).
  CAS PubMed Google Scholar
• Hajkova, P. et al. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452, 877–881 (2008). A comprehensive study of the dynamic changes of a range of epigenetic modifications during germ cell development.
  CAS PubMed Google Scholar
• Seki, Y. et al. Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice. Development 134, 2627–2638 (2007).
  CAS PubMed Google Scholar
• Seki, Y. et al. Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev. Biol. 278, 440–458 (2005).
  CAS PubMed Google Scholar
• Hajkova, P. et al. Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117, 15–23 (2002).
  CAS PubMed Google Scholar
• Ancelin, K. et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nature Cell Biol. 8, 623–630 (2006).
  CAS PubMed Google Scholar
• Morgan, H. D., Dean, W., Coker, H. A., Reik, W. & Petersen-Mahrt, S. K. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J. Biol. Chem. 279, 52353–52360 (2004).
  CAS Google Scholar
• Barreto, G. et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445, 671–675 (2007).
  CAS PubMed Google Scholar
• Gehring, M., Reik, W. & Henikoff, S. DNA demethylation by DNA repair. Trends Genet. 25, 82–90 (2009).
  CAS PubMed Google Scholar
• Huh, J. H., Bauer, M. J., Hsieh, T. F. & Fischer, R. L. Cellular programming of plant gene imprinting. Cell 132, 735–744 (2008).
  CAS PubMed Google Scholar
• Rai, K. et al. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135, 1201–1212 (2008).
  CAS PubMed PubMed Central Google Scholar
• Govin, J. et al. Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis. J. Cell Biol. 176, 283–294 (2007).
  CAS PubMed PubMed Central Google Scholar
• Martens, J. H. et al. The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J. 24, 800–812 (2005).
  CAS PubMed PubMed Central Google Scholar
• Peters, A. H. et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323–337 (2001).
  CAS PubMed Google Scholar
• Santos, F., Peters, A. H., Otte, A. P., Reik, W. & Dean, W. Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev. Biol. 280, 225–236 (2005).
  CAS PubMed Google Scholar
• van der Heijden, G. W. et al. Asymmetry in histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote. Mech. Dev. 122, 1008–1022 (2005).
  CAS PubMed Google Scholar
• Puschendorf, M. et al. PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nature Genet. 40, 411–420 (2008).
  CAS PubMed Google Scholar
• Probst, A. V., Santos, F., Reik, W., Almouzni, G. & Dean, W. Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygote. Chromosoma 116, 403–415 (2007).
  PubMed Google Scholar
• Monk, M., Boubelik, M. & Lehnert, S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99, 371–382 (1987).
  CAS PubMed Google Scholar
• Rougier, N. et al. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev. 12, 2108–2113 (1998).
  CAS PubMed PubMed Central Google Scholar
• Howlett, S. K. & Reik, W. Methylation levels of maternal and paternal genomes during preimplantation development. Development 113, 119–127 (1991).
  CAS PubMed Google Scholar
• Edwards, C. A. & Ferguson-Smith, A. C. Mechanisms regulating imprinted genes in clusters. Curr. Opin. Cell Biol. 19, 281–289 (2007).
  CAS PubMed Google Scholar
• Lane, N. et al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35, 88–93 (2003).
  CAS PubMed Google Scholar
• Chapman, V., Forrester, L., Sanford, J., Hastie, N. & Rossant, J. Cell lineage-specific undermethylation of mouse repetitive DNA. Nature 307, 284–286 (1984).
  CAS PubMed Google Scholar
• Rossant, J., Sanford, J. P., Chapman, V. M. & Andrews, G. K. Undermethylation of structural gene sequences in extraembryonic lineages of the mouse. Dev. Biol. 117, 567–573 (1986).
  CAS PubMed Google Scholar
• Farthing, C. R. et al. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 4, e1000116 (2008).
  PubMed PubMed Central Google Scholar
• Tanaka, T. S. et al. Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res. 12, 1921–1928 (2002).
  CAS PubMed PubMed Central Google Scholar
• Morgan, H. D., Santos, F., Green, K., Dean, W. & Reik, W. Epigenetic reprogramming in mammals. Hum. Mol. Genet. 14, R47–R58 (2005).
  CAS PubMed Google Scholar
• Erhardt, S. et al. Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Development 130, 4235–4248 (2003).
  CAS PubMed Google Scholar
• Sarmento, O. F. et al. Dynamic alterations of specific histone modifications during early murine development. J. Cell Sci. 117, 4449–4459 (2004).
  CAS PubMed Google Scholar
• Matsui, Y., Zsebo, K. & Hogan, B. L. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70, 841–847 (1992).
  CAS PubMed Google Scholar
• Resnick, J. L., Bixler, L. S., Cheng, L. & Donovan, P. J. Long-term proliferation of mouse primordial germ cells in culture. Nature 359, 550–551 (1992).
  CAS PubMed Google Scholar
• Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156 (1981). Pioneering work that describes the first derivation of pluripotent, self-renewing embryonic stem cells in mice.
  CAS PubMed Google Scholar
• Tesar, P. J. Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos. Proc. Natl Acad. Sci. USA 102, 8239–8244 (2005).
  CAS PubMed PubMed Central Google Scholar
• Brons, I. G. et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195 (2007).
  CAS PubMed Google Scholar
• Tesar, P. J. et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448, 196–199 (2007). References 48 and 49 identify a pluripotent cell population in the post-implantation epiblast that can give rise to self-renewing epiblast stem cells with unique characteristics compared with ES cells.
  CAS PubMed Google Scholar
• Durcova-Hills, G., Tang, F., Doody, G., Tooze, R. & Surani, M. A. Reprogramming primordial germ cells into pluripotent stem cells. PLoS ONE 3, e3531 (2008).
  PubMed PubMed Central Google Scholar
• Niwa, H. How is pluripotency determined and maintained? Development 134, 635–646 (2007).
  CAS PubMed Google Scholar
• Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genet. 38, 431–440 (2006). One of the first large-scale chromatin immunoprecipitation screens identifying the transcriptional network established by the pluripotency factors OCT4 and NANOG in mouse ES cells.
  CAS PubMed Google Scholar
• Sharov, A. A. et al. Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data. BMC Genomics 9, 269 (2008).
  PubMed PubMed Central Google Scholar
• Zhang, J. et al. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nature Cell Biol. 8, 1114–1123 (2006).
  CAS PubMed Google Scholar
• Wu, Q. et al. Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J. Biol. Chem. 281, 24090–24094 (2006).
  CAS PubMed Google Scholar
• Lim, C. Y. et al. Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 3, 543–554 (2008).
  CAS PubMed Google Scholar
• Yang, J. et al. Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells. Proc. Natl Acad. Sci. USA 105, 19756–19761 (2008).
  CAS PubMed PubMed Central Google Scholar
• Chew, J. L. et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol. Cell. Biol. 25, 6031–6046 (2005).
  CAS PubMed PubMed Central Google Scholar
• Rodda, D. J. et al. Transcriptional regulation of Nanog by OCT4 and SOX2. J. Biol. Chem. 280, 24731–24737 (2005).
  CAS PubMed Google Scholar
• Liang, J. et al. Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nature Cell Biol. 10, 731–739 (2008).
  CAS PubMed Google Scholar
• Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349–353 (2006). Genome-wide profile of the target genes of PcG proteins that identifies that PcG proteins repress a large cohort of developmental regulators in ES cells, the expression of which would otherwise promote differentiation.
  CAS PubMed Google Scholar
• Lee, T. I. et al. Control of developmental regulators by polycomb in human embryonic stem cells. Cell 125, 301–313 (2006).
  CAS PubMed PubMed Central Google Scholar
• Azuara, V. et al. Chromatin signatures of pluripotent cell lines. Nature Cell Biol. 8, 532–538 (2006).
  CAS PubMed Google Scholar
• Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006). References 63 and 64 found independently that genes required for later development are in a poised state for activation, which is characterized by bivalent chromatin domains that consist of active (H3K4me3) and repressive (H3K27me3) marks.
  CAS PubMed Google Scholar
• Mikkelsen, T. S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).
  CAS PubMed PubMed Central Google Scholar
• Fouse, S. D. et al. Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. Cell Stem Cell 2, 160–169 (2008).
  CAS PubMed PubMed Central Google Scholar
• Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766–770 (2008).
  CAS PubMed PubMed Central Google Scholar
• Ura, H. et al. STAT3 and Oct-3/4 control histone modification through induction of Eed in embryonic stem cells. J. Biol. Chem. 283, 9713–9723 (2008).
  CAS PubMed 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).
  CAS PubMed PubMed Central Google Scholar
• Feldman, N. et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nature Cell Biol. 8, 188–194 (2006).
  CAS PubMed Google Scholar
• Epsztejn-Litman, S. et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nature Struct. Mol. Biol. 15, 1176–1183 (2008).
  CAS Google Scholar
• Hattori, N. et al. Epigenetic regulation of Nanog gene in embryonic stem and trophoblast stem cells. Genes Cells 12, 387–396 (2007).
  CAS PubMed Google Scholar
• Li, J. Y. et al. Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Mol. Cell. Biol. 27, 8748–8759 (2007).
  CAS PubMed PubMed Central Google Scholar
• Dietrich, J. E. & Hiiragi, T. Stochastic patterning in the mouse pre-implantation embryo. Development 134, 4219–4231 (2007). A detailed investigation of the expression of lineage-determining transcription factors in the early mouse embryo that shows the stochasticity of their expression until the mid-to-late blastocyst stage.
  CAS PubMed Google Scholar
• Ralston, A. & Rossant, J. Cdx2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo. Dev. Biol. 313, 614–629 (2008).
  CAS PubMed Google Scholar
• Jedrusik, A. et al. Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo. Genes Dev. 22, 2692–2706 (2008).
  CAS PubMed PubMed Central Google Scholar
• Hayashi, K., Lopes, S. M., Tang, F. & Surani, M. A. Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states. Cell Stem Cell 3, 391–401 (2008). ES cells fluctuate in their expression of developmental key genes, such as Stella , and these STELLA-positive and STELLA-negative subpopulations, although epigenetically and functionally distinct, are interconvertible.
  CAS PubMed Google Scholar
• Chambers, I. et al. Nanog safeguards pluripotency and mediates germline development. Nature 450, 1230–1234 (2007).
  CAS PubMed Google Scholar
• Cui, L. et al. Spatial distribution and initial changes of SSEA-1 and other cell adhesion-related molecules on mouse embryonic stem cells before and during differentiation. J. Histochem. Cytochem. 52, 1447–1457 (2004).
  CAS PubMed PubMed Central Google Scholar
• Furusawa, T., Ohkoshi, K., Honda, C., Takahashi, S. & Tokunaga, T. Embryonic stem cells expressing both platelet endothelial cell adhesion molecule-1 and stage-specific embryonic antigen-1 differentiate predominantly into epiblast cells in a chimeric embryo. Biol. Reprod. 70, 1452–1457 (2004).
  CAS PubMed Google Scholar
• Payer, B. et al. Generation of stella–GFP transgenic mice: a novel tool to study germ cell development. Genesis 44, 75–83 (2006).
  CAS PubMed Google Scholar
• Toyooka, Y., Shimosato, D., Murakami, K., Takahashi, K. & Niwa, H. Identification and characterization of subpopulations in undifferentiated ES cell culture. Development 135, 909–918 (2008).
  CAS PubMed Google Scholar
• Zernicka-Goetz, M. The first cell-fate decisions in the mouse embryo: destiny is a matter of both chance and choice. Curr. Opin. Genet. Dev. 16, 406–412 (2006).
  CAS PubMed Google Scholar
• Rossant, J. & Tam, P. P. Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development 136, 701–713 (2009).
  CAS PubMed Google Scholar
• Niwa, H., Miyazaki, J. & Smith, A. G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genet. 24, 372–376 (2000).
  CAS PubMed Google Scholar
• Mitsui, K. et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631–642 (2003).
  CAS PubMed Google Scholar
• Niwa, H. et al. Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell 123, 917–929 (2005). An important concept in the cell lineage specification process is the mutual inhibitory interaction of transcription factors with opposing functions.
  CAS PubMed Google Scholar
• Nishioka, N. et al. Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech. Dev. 125, 270–283 (2008).
  CAS PubMed Google Scholar
• Yagi, R. et al. Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development. Development 134, 3827–3836 (2007).
  CAS PubMed Google Scholar
• Donnison, M. et al. Loss of the extraembryonic ectoderm in Elf5 mutants leads to defects in embryonic patterning. Development 132, 2299–2308 (2005).
  CAS PubMed Google Scholar
• Ng, R. K. et al. Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5. Nature Cell Biol. 10, 1280–1290 (2008). DNA methylation establishes a major epigenetic restriction of cell lineage fate by regulating the trophoblast-reinforcing gatekeeper gene Elf5 .
  CAS PubMed Google Scholar
• Dodge, J. E., Kang, Y. K., Beppu, H., Lei, H. & Li, E. Histone H3-K9 methyltransferase ESET is essential for early development. Mol. Cell. Biol. 24, 2478–2486 (2004).
  CAS PubMed PubMed Central Google Scholar
• O'Carroll, D. et al. The polycomb-group gene Ezh2 is required for early mouse development. Mol. Cell. Biol. 21, 4330–4336 (2001).
  CAS PubMed PubMed Central Google Scholar
• Torres-Padilla, M. E., Parfitt, D. E., Kouzarides, T. & Zernicka-Goetz, M. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature 445, 214–218 (2007).
  CAS PubMed PubMed Central Google Scholar
• Yamanaka, Y., Ralston, A., Stephenson, R. O. & Rossant, J. Cell and molecular regulation of the mouse blastocyst. Dev. Dyn. 235, 2301–2314 (2006).
  CAS PubMed Google Scholar
• Nishioka, N. et al. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16, 398–410 (2009).
  CAS PubMed Google Scholar
• Hirasawa, R. & Sasaki, H. Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos. Gene Expr. Patterns 9, 27–30 (2009).
  CAS PubMed Google Scholar
• Watanabe, D., Suetake, I., Tada, T. & Tajima, S. Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech. Dev. 118, 187–190 (2002).
  CAS PubMed Google Scholar
• Waddington, C. H. Organisers and Genes (Cambridge Univ. Press, Cambridge, UK, 1940).
  Google Scholar
• Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006). The first groundbreaking report of the derivation of ES cell-like iPS cells from terminally differentiated adult fibroblasts.
  CAS PubMed Google Scholar
• Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
  CAS PubMed Google Scholar
• Meissner, A., Wernig, M. & Jaenisch, R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nature Biotechnol. 25, 1177–1181 (2007).
  CAS Google Scholar
• Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. & Yamanaka, S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949–953 (2008).
  CAS PubMed Google Scholar
• Feng, B. et al. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nature Cell Biol. 11, 197–203 (2009).
  CAS PubMed Google Scholar
• Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).
  CAS PubMed Google Scholar
• Mikkelsen, T. S. et al. Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49–55 (2008).
  CAS PubMed PubMed Central Google Scholar
• Shi, Y. et al. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525–528 (2008).
  CAS PubMed Google Scholar
• Huangfu, D. et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnol. 26, 795–797 (2008).
  CAS Google Scholar
• Chang, H. H., Hemberg, M., Barahona, M., Ingber, D. E. & Huang, S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 453, 544–547 (2008). Gene expression noise causes fluctuations in protein levels that produce persistent cell individuality in clonal populations. This stochasticity can drive lineage specification.
  CAS PubMed PubMed Central Google Scholar
• MacArthur, B. D., Please, C. P. & Oreffo, R. O. Stochasticity and the molecular mechanisms of induced pluripotency. PLoS ONE 3, e3086 (2008). Computational modelling of how the positive interference of stochastic gene expression levels can lead to lineage choice and enables reprogramming to iPS cells.
  PubMed PubMed Central Google Scholar
• Slotkin, R. K. et al. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell 136, 461–472 (2009).
  CAS PubMed PubMed Central Google Scholar
• Wang, J. et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nature Genet. 41, 125–129 (2009).
  CAS PubMed Google Scholar
• Ayoub, N., Jeyasekharan, A. D., Bernal, J. A. & Venkitaraman, A. R. HP1-β mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453, 682–686 (2008).
  CAS PubMed Google Scholar
• Chin, H. G. et al. Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res. 35, 7313–7323 (2007).
  CAS PubMed PubMed Central Google Scholar
• Wei, F., Scholer, H. R. & Atchison, M. L. Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J. Biol. Chem. 282, 21551–21560 (2007).
  CAS PubMed Google Scholar
• Cardoso, M. C. & Leonhardt, H. DNA methyltransferase is actively retained in the cytoplasm during early development. J. Cell Biol. 147, 25–32 (1999).
  CAS PubMed PubMed Central Google Scholar
• Tanaka, S., Kunath, T., Hadjantonakis, A. K., Nagy, A. & Rossant, J. Promotion of trophoblast stem cell proliferation by FGF4. Science 282, 2072–2075 (1998). The successful derivation and maintenance of stem cells of the trophoblast lineage that retain the established lineage restriction and contribute exclusively to placental structures in chimeras.
  CAS PubMed Google Scholar
• Kunath, T. et al. Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts. Development 132, 1649–1661 (2005).
  CAS PubMed Google Scholar
• Yeom, Y. I. et al. Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 122, 881–894 (1996).
  CAS PubMed Google Scholar
• Avilion, A. A. et al. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 17, 126–140 (2003).
  CAS PubMed PubMed Central Google Scholar
• Elling, U., Klasen, C., Eisenberger, T., Anlag, K. & Treier, M. Murine inner cell mass-derived lineages depend on Sall4 function. Proc. Natl Acad. Sci. USA 103, 16319–16324 (2006).
  CAS PubMed PubMed Central Google Scholar
• Payer, B. et al. Stella is a maternal effect gene required for normal early development in mice. Curr. Biol. 13, 2110–2117 (2003).
  CAS PubMed Google Scholar
• Strumpf, D. et al. Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development 132, 2093–2102 (2005).
  CAS PubMed Google Scholar
• McConnell, J., Petrie, L., Stennard, F., Ryan, K. & Nichols, J. Eomesodermin is expressed in mouse oocytes and pre-implantation embryos. Mol. Reprod. Dev. 71, 399–404 (2005).
  CAS PubMed Google Scholar
• Uy, G. D., Downs, K. M. & Gardner, R. L. Inhibition of trophoblast stem cell potential in chorionic ectoderm coincides with occlusion of the ectoplacental cavity in the mouse. Development 129, 3913–3924 (2002).
  CAS PubMed Google Scholar