Biomaterial Database

The intrinsic and extrinsic effects of TET proteins during gastrulation. 2022

Saifeng Cheng, and Markus Mittnenzweig, and Yoav Mayshar, and Aviezer Lifshitz, and Marko Dunjić, and Yoach Rais, and Raz Ben-Yair, and Stephanie Gehrs, and Elad Chomsky, and Zohar Mukamel, and Hernan Rubinstein, and Katharina Schlereth, and Netta Reines, and Ayelet-Hashahar Orenbuch, and Amos Tanay, and Yonatan Stelzer

Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel.

Mice deficient for all ten-eleven translocation (TET) genes exhibit early gastrulation lethality. However, separating cause and effect in such embryonic failure is challenging. To isolate cell-autonomous effects of TET loss, we used temporal single-cell atlases from embryos with partial or complete mutant contributions. Strikingly, when developing within a wild-type embryo, Tet-mutant cells retain near-complete differentiation potential, whereas embryos solely comprising mutant cells are defective in epiblast to ectoderm transition with degenerated mesoderm potential. We map de-repressions of early epiblast factors (e.g., Dppa4 and Gdf3) and failure to activate multiple signaling from nascent mesoderm (Lefty, FGF, and Notch) as likely cell-intrinsic drivers of TET loss phenotypes. We further suggest loss of enhancer demethylation as the underlying mechanism. Collectively, our work demonstrates an unbiased approach for defining intrinsic and extrinsic embryonic gene function based on temporal differentiation atlases and disentangles the intracellular effects of the demethylation machinery from its broader tissue-level ramifications.

UI	MeSH Term	Description	Entries
D008648	Mesoderm	The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.	Mesenchyme,Dorsal Mesoderm,Intermediate Mesoderm,Lateral Plate Mesoderm,Mesenchyma,Paraxial Mesoderm,Dorsal Mesoderms,Intermediate Mesoderms,Lateral Plate Mesoderms,Mesenchymas,Mesoderm, Dorsal,Mesoderm, Intermediate,Mesoderm, Lateral Plate,Mesoderm, Paraxial,Mesoderms, Dorsal,Mesoderms, Intermediate,Mesoderms, Lateral Plate,Mesoderms, Paraxial,Paraxial Mesoderms,Plate Mesoderm, Lateral,Plate Mesoderms, Lateral
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
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
D004622	Embryo, Mammalian	The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.	Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
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
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
D054262	Gastrulation	A process of complicated morphogenetic cell movements that reorganizes a bilayer embryo into one with three GERM LAYERS and specific orientation (dorsal/ventral; anterior/posterior). Gastrulation describes the germ layer development of a non-mammalian BLASTULA or that of a mammalian BLASTOCYST.
D018507	Gene Expression Regulation, Developmental	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.	Developmental Gene Expression Regulation,Embryologic Gene Expression Regulation,Gene Expression Regulation, Embryologic,Regulation of Gene Expression, Developmental,Regulation of Gene Expression, Embryologic,Regulation, Gene Expression, Developmental,Regulation, Gene Expression, Embryologic