Tet1 Is Dispensable for Maintaining Pluripotency and Its Loss Is Compatible with Embryonic and Postnatal Development
Autor: | Styliani Markoulaki, Meelad M. Dawlaty, Jongpil Kim, Qing Gao, Yueh-Chiang Hu, Kibibi Ganz, Sang-Woon Choi, Rudolf Jaenisch, Albert W. Cheng, David C. Page, Benjamin E. Powell |
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Rok vydání: | 2011 |
Předmět: |
Pluripotent Stem Cells
Mutant Embryonic Development Biology Article Cytosine Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Proto-Oncogene Proteins Genetics Animals Body Size Induced pluripotent stem cell Embryonic Stem Cells 030304 developmental biology Regulation of gene expression 0303 health sciences Tetraploid complementation assay Genetic Complementation Test Embryogenesis Gene Expression Regulation Developmental Embryo Cell Biology DNA Methylation Embryo Mammalian Molecular biology Embryonic stem cell Cell biology DNA-Binding Proteins Mice Inbred C57BL Tetraploidy Fertility Animals Newborn DNA methylation 5-Methylcytosine Molecular Medicine Female 030217 neurology & neurosurgery |
Zdroj: | Cell Stem Cell. 9(2):166-175 |
ISSN: | 1934-5909 |
DOI: | 10.1016/j.stem.2011.07.010 |
Popis: | Summary The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1 −/− ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development. |
Databáze: | OpenAIRE |
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