T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications

Lluı́s, Frederic; Ombrato, Luigi; Pedone, Elisa; Pepe, Stefano; Merrill, Bradley J.; Cosma, María Pía

doi:10.1073/pnas.1017402108

Cited by 51 publications

(59 citation statements)

References 28 publications

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“…Tcf3 -/-mouse ES cells show increased NANOG expression and do not undergo efficient differentiation in standard conditions, consistent with the view that TCF3 is a negative regulator of the ES cell pluripotency network (Cole et al, 2008;Pereira et al, 2006;Tam et al, 2008;Yi et al, 2008). In fact, TCF3 has been identified as an inhibitor of pluripotency in unbiased forward genetic screens in mouse ES cells (Guo et al, 2011;Schaniel et al, 2009) and during cell reprogramming (Han et al, 2010;Lluis et al, 2011). The majority of the genes repressed by TCF3 differ from those activated in response to Wnt proteins, indicating that TCF3 might have Wntindependent functions (Cole et al, 2008;Merrill et al, 2004;Nguyen et al, 2006;Yi et al, 2011).…”

Section: Inactivation Of Tcf3-mediated Repression By Wnt Signalingsupporting

confidence: 53%

Maintaining embryonic stem cell pluripotency with Wnt signaling

2011

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SummaryWnt signaling pathways control lineage specification in vertebrate embryos and regulate pluripotency in embryonic stem (ES) cells, but how the balance between progenitor selfrenewal and differentiation is achieved during axis specification and tissue patterning remains highly controversial. The context-and stage-specific effects of the different Wnt pathways produce complex and sometimes opposite outcomes that help to generate embryonic cell diversity. Although the results of recent studies of the Wnt/-catenin pathway in ES cells appear to be surprising and controversial, they converge on the same conserved mechanism that leads to the inactivation of TCF3-mediated repression.Key words: Embryonic stem cells, TCF, -catenin, GSK3, Pluripotency, Self-renewal, Homeodomain-interacting protein kinase Introduction A major goal of developmental and stem cell biology is to elucidate the mechanisms that allow embryonic progenitor cells to choose a specific path for differentiation or to maintain their pluripotency. Pluripotency is a common attribute of the early blastomeres of vertebrates, and is one that allows these cells to contribute to any of the three germ layers (ectoderm, mesoderm or endoderm). The derivation of pluripotent and self-renewing embryonic stem (ES) cells in the early 1980s established one of the best in vitro models of early embryonic development (Evans and Kaufman, 1981;Martin, 1981). Nevertheless, our understanding of the key pathways that lead to the ES cell-like state is far from complete, mainly due to the fact that normal blastocyst cells do not undergo the unlimited self-renewal that is observed in ES cell culture. The question of how a blastocyst cell is able to differentiate into a cell that belongs to any of the three germ layers remains unclear. However, recent progress has provided some insight into this question, with the identification of several signaling pathways that are crucial for lineage specification in the early embryo and in ES cells (Arnold and Robertson, 2009;Boyer et al., 2005;Nichols and Smith, 2011;Rossant and Tam, 2009;Schier and Talbot, 2005;Ying et al., 2008).Another critically important process in the embryo is the acquisition by cells of positional information. In the simplest case, this information corresponds to the specification of axes in the whole embryo and in specific organs. Proper positional values are essential for normal embryogenesis and need to be reconstituted during regeneration for proper organ function (Brockes and Kumar, 2008;Kragl et al., 2009). Whereas animal pole blastomeres of the Xenopus embryo appear to 'remember' their position in the embryo from which they originated (Savage and Phillips, 1989;Sokol and Melton, 1991), there is no clear evidence that such positional information exists within the mammalian blastocyst from which ES cells are derived (Arnold and Robertson, 2009;Gardner et al., 1992;Rossant and Tam, 2009). Nevertheless, some studies argue that such information can arise by a stochastic mechanism de novo, during formation o...

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Section: Inactivation Of Tcf3-mediated Repression By Wnt Signalingsupporting

confidence: 53%

Maintaining embryonic stem cell pluripotency with Wnt signaling

2011

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“…55 Upon fusion with neural progenitor cells (NPCs), Tcf3 -/-ESCs produce a high number of reprogrammed hybrids as compared with the fusion of NPCs with wtESCs. Also, when the levels of Tcf3 in ESCs was reduced by RNA interference, after fusion, these cells were able to reprogram MEFs.…”

Section: Gsk3mentioning

confidence: 99%

“…Tcf4 (Tcf7l2) and Lef-1 are scarcely expressed. 55,56 Mainly for this reason, the most studied Tcf protein in ESCs is Tcf3, which has two different isoforms in ESCs. 57,58 In addition, and importantly, Tcf3 is an integral component of the Oct4/Sox2/Nanog self-renewal circuit.…”

Section: Gsk3mentioning

confidence: 99%

Regulation of self-renewal and reprogramming by TCF factors

Ombrato¹,

Lluı́s²,

Cosma³

2012

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“…Adding to this complexity in vertebrate systems is the likelihood that different target genes will require different TCFs for regulation. For example, loss of TCF3 in a neuroblast stem cell results in global elevation of H3/ H4ac levels (Lluis et al 2011), a change consistent with its role in transcriptional repression. Perhaps targets that are more dependent on TCF3 will also show larger differences in histone acetylation in response to pathway activation.…”

Section: Km Cadigan and ML Watermanmentioning

confidence: 99%