Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development

Meelad M. Dawlaty, Kibibi Ganz, Benjamin E. Powell, Yueh Chiang Hu, Styliani Markoulaki, Albert W. Cheng, Qing Gao, Jongpil Kim, Sang Woon Choi, David C. Page, Rudolf Jaenisch

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)166-175
Number of pages10
JournalCell Stem Cell
Volume9
Issue number2
DOIs
StatePublished - Aug 5 2011
Externally publishedYes

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Embryonic Development
5-Methylcytosine
Tetraploidy
Body Size
Maintenance
Parturition
Gene Expression
5-hydroxymethylcytosine
Enzymes
In Vitro Techniques
Mouse Embryonic Stem Cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. / Dawlaty, Meelad M.; Ganz, Kibibi; Powell, Benjamin E.; Hu, Yueh Chiang; Markoulaki, Styliani; Cheng, Albert W.; Gao, Qing; Kim, Jongpil; Choi, Sang Woon; Page, David C.; Jaenisch, Rudolf.

In: Cell Stem Cell, Vol. 9, No. 2, 05.08.2011, p. 166-175.

Research output: Contribution to journalArticle

Dawlaty, MM, Ganz, K, Powell, BE, Hu, YC, Markoulaki, S, Cheng, AW, Gao, Q, Kim, J, Choi, SW, Page, DC & Jaenisch, R 2011, 'Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development', Cell Stem Cell, vol. 9, no. 2, pp. 166-175. https://doi.org/10.1016/j.stem.2011.07.010
Dawlaty, Meelad M. ; Ganz, Kibibi ; Powell, Benjamin E. ; Hu, Yueh Chiang ; Markoulaki, Styliani ; Cheng, Albert W. ; Gao, Qing ; Kim, Jongpil ; Choi, Sang Woon ; Page, David C. ; Jaenisch, Rudolf. / Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. In: Cell Stem Cell. 2011 ; Vol. 9, No. 2. pp. 166-175.
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