Biomaterial Database

Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling. 2010

Taeko Kobayashi, and Ryoichiro Kageyama

Institute for Virus Research, Kyoto University, Japan. tkobayas@virus.kyoto-u.ac.jp

Embryonic stem (ES) cells display heterogeneous responses upon induction of differentiation. Recent analysis has shown that Hes1 expression oscillates with a period of about 3-5 h in mouse ES cells and that this oscillating expression contributes to the heterogeneous responses: Hes1-high ES cells are prone to the mesodermal fate, while Hes1-low ES cells are prone to the neural fate. These outcomes of Hes1-high and Hes1-low ES cells are very similar to those of inactivation and activation of Notch signaling, respectively. These results suggest that Hes1 and Notch signaling lead to opposite outcomes in ES cell differentiation, although they work in the same direction in most other cell types. Here, we found that Hes1 acts as an inhibitor but not as an effector of Notch signaling in ES cell differentiation. Our results indicate that sustained Hes1 expression delays the differentiation of ES cells and promotes the preference for the mesodermal rather than the neural fate by suppression of Notch signaling.

UI	MeSH Term	Description	Entries
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000072056	Transcription Factor HES-1	A basic-helix-loop-helix transcription factor that functions as a transcriptional repressor for genes transcribed by bHLH proteins. For example, it may negatively regulate MYOGENESIS by inhibiting MyoD1 and ASH1 proteins. It is also required for the stability of FANCONI ANEMIA COMPLEMENTATION GROUP PROTEINS and their localization to the cell nucleus in response to DNA DAMAGE.	Hairy and Enhancer of Split 1 Protein,Hairy-Like Transcription Factor,HES-1, Transcription Factor,Hairy Like Transcription Factor,Transcription Factor HES 1,Transcription Factor, Hairy-Like
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051792	Basic Helix-Loop-Helix Transcription Factors	A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.	Basic Helix-Loop-Helix Transcription Factor,bHLH Protein,bHLH Transcription Factor,bHLH Proteins,bHLH Transcription Factors,Basic Helix Loop Helix Transcription Factor,Basic Helix Loop Helix Transcription Factors,Factor, bHLH Transcription,Protein, bHLH,Transcription Factor, bHLH,Transcription Factors, bHLH
D051880	Receptors, Notch	A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors.	Notch Protein,Notch Receptor,Notch Receptors,Notch Proteins,Protein, Notch,Receptor, Notch
D053595	Embryonic Stem Cells	Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.	Stem Cells, Embryonic,Cell, Embryonic Stem,Cells, Embryonic Stem,Embryonic Stem Cell,Stem Cell, Embryonic
D018398	Homeodomain Proteins	Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).	Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic