Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Direct Conversion of Trophoblast Stem Cells into Pluripotent Stem Cells by Oct4

ABSTRACT: Embryonic stem (ES) cells and trophoblast stem (TS) cells are both derived from early embryos, yet these cells have distinct differentiation properties. ES cells can differentiate into all three germ layer cell types, whereas TS cells can only differentiate into placental cells. It has not been determined whether TS cells can be converted into ES-like pluripotent stem (PS) cells. Here we report that overexpression of a single transcription factor, Oct4, in TS cells is sufficient to convert TS cells into a pluripotent state. These Oct4 induced pluripotent stem (OiPS) cells have the epigenetic characteristics of ES cells, including X chromosome reactivation and elevated H3K27 me3 modifications. The gene expression profile of OiPS cells and ES cells was very similar. Moreover, OiPS cells can differentiate into the three germ layer cell types in vitro and in vivo. More importantly, chimeric mice with germline transmission could be efficiently produced from OiPS cells. To our knowledge, this is the first evidence showing that only one single transcription factor could convert the non-embryonic TS cells into pluripotent stem cells with pluripotency. Gene expression profile of iPS cells and trophoblast stem cells were generated by Affymetrix Mouse Gene 1.0 ST Array. The Gene expression profile of ES cell R1 in GSE17004 was used as control. Three biological repeats were included for each line.

ORGANISM(S): Mus musculus

SUBMITTER: Tong Wu

PROVIDER: E-GEOD-25255 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:TET-family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem (ES) cells. ES cells depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1, and display hyperactive Nodal signalling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions that favor derivation of trophoblast stem (TS) cells, Tet1-depleted ES cells activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in mid-gestation embryo chimeras. Consistent with these findings, Tet1-depleted ES cells form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm and ectopic appearance of trophoblastic giant cells. Thus Tet1 functions to regulate the lineage differentiation potential of ES cells. Here, we performed whole-genome transcriptome profiling of ES cells stably depleted of Tet1 by shRNA knockdown (Tet1-kd) cultured in either standard ES cell or in TS cell culture conditions. Gene expression changes in Tet1-kd ES cells were fairly modest compared to control (GFP-kd) cells, although gene ontology (GO) analysis of differentially expressed genes yielded many terms related to embryonic development and cell cycle regulation. In TS cell culture conditions, a core set of genes defining trophectodermal cell differentiation, including Cdx2, Eomes and Tead4, was enriched in Tet1-kd compared to GFP-kd cells. A total of 27 samples were analysed with at least 3 replicates in each group. Control/reference samples comprise ES cells cultured in standard ES cell media (true ES cells) and TS cells cultured in Fgf4/heparin-supplemented (TS) media (true TS cells). We compared Tet1-kd ES cells with GFP-kd ES cells cultured in either ES or TS cell media. In addition, we included a set of Tet1-kd subclones (Tet1-kd-sc) cultured in TS cell condition and a set of untransfected ES cells (parental control) cultured in TS cell condition.

Dataset Information

Direct Conversion of Trophoblast Stem Cells into Pluripotent Stem Cells by Oct4

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets