Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Schroeder, Timm; Fraser, Stuart T.; Ogawa, Michio; Nishikawa, Satomi; Oka, Chio; Bornkamm, Georg W.; Nishikawa, Shin Ichi; Honjo, Tasuku; Just, Ursula

doi:10.1073/pnas.0438008100

Cited by 112 publications

(107 citation statements)

References 42 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26 Vice versa, blockage of Notch signaling in RBP-J-deficient ES cells results in enhanced mesodermal and cardiogenic specification 34 and expression of a dominant negative mutant of RBP-J, incapable of DNA binding, forces cardiogenesis. 29 Furthermore, in the presence of appropriate other signals that support neuronal differentiation, Notch signaling drives ESCs towards the neuro-ectodermal lineages.…”

Section: Discussionmentioning

confidence: 99%

Notch1 signaling regulates chondrogenic lineage determination through Sox9 activation

et al. 2011

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Notch1 signaling regulates chondrogenic lineage determination through Sox9 activation

et al. 2011

View full text Add to dashboard Cite

“…1a,b). Differentiation of ES cells to macrophages was started by cocultivation of ES cells on OP9 stroma cells (Nakano et al 1994) as described (Schroeder et al 2003). At day 8 of differentiation, suspension cells were transferred to cell culture flasks using medium containing macrophage colony-stimulating factor (M-CSF) and interleukin 3 (IL-3).…”

Section: Cellsmentioning

confidence: 99%

Three-dimensional positioning of genes in mouse cell nuclei

et al. 2008

View full text Add to dashboard Cite

To understand the regulation of the genome, it is necessary to understand its three-dimensional organization in the nucleus. We investigated the positioning of eight gene loci on four different chromosomes, including the β-globin gene, in mouse embryonic stem cells and in in vitro differentiated macrophages by fluorescence in situ hybridization on structurally preserved nuclei, confocal microscopy, and 3D quantitative image analysis. We found that gene loci on the same chromosome can significantly differ from each other and from their chromosome territory in their average radial nuclear position. Radial distribution of a given gene locus can change significantly between cell types, excluding the possibility that positioning is determined solely by the DNA sequence. For the set of investigated gene loci, we found no relationship between radial distribution and local gene density, as it was described for human cell nuclei. We did find, however, correlation with other genomic properties such as GC content and certain repetitive elements such as long terminal repeats or long interspersed nuclear elements. Our results suggest that gene density itself is not a driving force in nuclear positioning. Instead, we propose that other genomic properties play a role in determining nuclear chromatin distribution.

show abstract

“…Constitutive expression of NICD in mESCs or treatment of hESCs with DLL1-expressing feeders favours the acquisition of a neurectodermal fate (Das et al, 2010;Kurpinski et al, 2010;Lowell et al, 2006). By contrast, inactivation of the NOTCH pathway with a γ-SECRETASE inhibitor or via genetic deletion of Notch1 and Rbpj accelerates ESC differentiation towards mesoderm, and enhances their cardiogenic potential (Jang et al, 2008;Nemir et al, 2006;Schroeder et al, 2003). Further revealing the complexity of NOTCH signalling, ligand-dependent cell type specification was observed when mESCs were exposed to JAG1 or DLL4 (Ramasamy and Lenka, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Inducible activation of NICD in mESCs cultured under mesoderm differentiation conditions leads to a reduction of endothelial, haematopoietic and cardiac differentiation and favours the generation of smooth muscle cells (SMC) (Nemir et al, 2006;Schroeder et al, 2003Schroeder et al, , 2006. Activation of the NOTCH pathway in human mesenchymal or ESCs similarly induces SMC differentiation (Kurpinski et al, 2010).…”

Section: Notch Signalling Regulates the Acquisition Of Distinct Mesodmentioning

confidence: 99%

“…NOTCH is dispensable for mESC and hESC self-renewal. Notch1 and Rbpj null mESCs can be established and maintained normally (Nemir et al, 2006;Schroeder et al, 2003) and blockade of the NOTCH pathway in hESCs by using a γ-SECRETASE inhibitor or a dominant negative form of MAML seems to enhance the growth of undifferentiated cells and to prevent their spontaneous differentiation (Noggle et al, 2006;Yu et al, 2008). However, canonical NOTCH signalling has been shown to regulate lineage commitment when ESCs are induced to differentiate.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

et al. 2015

View full text Add to dashboard Cite

NOTCH signalling is an evolutionarily conserved pathway involved in intercellular communication essential for cell fate choices during development. Although dispensable for early aspects of mouse development, canonical RBPJ-dependent NOTCH signalling has been shown to influence lineage commitment during embryonic stem cell (ESC) differentiation. NOTCH activation in ESCs promotes the acquisition of a neural fate, whereas its suppression favours their differentiation into cardiomyocytes. This suggests that NOTCH signalling is implicated in the acquisition of distinct embryonic fates at early stages of mammalian development. In order to investigate in vivo such a role for NOTCH signalling in shaping cell fate specification, we use genetic approaches to constitutively activate the NOTCH pathway in the mouse embryo. Early embryonic development, including the establishment of anterior-posterior polarity, is not perturbed by forced NOTCH activation. By contrast, widespread NOTCH activity in the epiblast triggers dramatic gastrulation defects. These are fully rescued in a RBPJ-deficient background. Epiblast-specific NOTCH activation induces acquisition of neurectoderm identity and disrupts the formation of specific mesodermal precursors including the derivatives of the anterior primitive streak, the mouse organiser. In addition, we show that forced NOTCH activation results in misregulation of NODAL signalling, a major determinant of early embryonic patterning. Our study reveals a previously unidentified role for canonical NOTCH signalling during mammalian gastrulation. It also exemplifies how in vivo studies can shed light on the mechanisms underlying cell fate specification during in vitro directed differentiation.

show abstract

Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Cited by 112 publications

References 42 publications

Notch1 signaling regulates chondrogenic lineage determination through Sox9 activation

Notch1 signaling regulates chondrogenic lineage determination through Sox9 activation

Three-dimensional positioning of genes in mouse cell nuclei

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

Contact Info

Product

Resources

About