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Establishment of trophoblast stem cell lines from somatic cell nuclear-transferred embryos

Mayumi Oda, Satoshi Tanaka, Yukiko Yamazaki, Hiroshi Ohta, Misa Iwatani, Masako Suzuki, Jun Ohgane, Naka Hattori, Ryuzo Yanagimachi, Teruhiko Wakayama, Kunio Shiota
Proceedings of the National Academy of Sciences of the United States of America 2009 September 22, 106 (38): 16293-7
19706390
Placental abnormalities occur frequently in cloned animals. Here, we attempted to isolate trophoblast stem (TS) cells from mouse blastocysts produced by somatic cell nuclear transfer (NT) at the blastocyst stage (NT blastocysts). Despite the predicted deficiency of the trophoblast cell lineage, we succeeded in isolating cell colonies with typical morphology of TS cells and cell lines from the NT blastocysts (ntTS cell lines) with efficiency as high as that from native blastocysts. The established 10 ntTS cell lines could be maintained in the undifferentiated state and induced to differentiate into several trophoblast subtypes in vitro. A comprehensive analysis of the transcriptional and epigenetic traits demonstrated that ntTS cells were indistinguishable from control TS cells. In addition, ntTS cells contributed exclusively to the placenta and survived until term in chimeras, indicating that ntTS cells have developmental potential as stem cells. Taken together, our data show that NT blastocysts contain cells that can produce TS cells in culture, suggesting that proper commitment to the trophoblast cell lineage in NT embryos occurs by the blastocyst stage.

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