Establishment of trophoblast stem cell lines from somatic cell nuclear-transferred embryos.
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.
Oda
Mayumi
M
Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Tanaka
Satoshi
S
Yamazaki
Yukiko
Y
Ohta
Hiroshi
H
Iwatani
Misa
M
Suzuki
Masako
M
Ohgane
Jun
J
Hattori
Naka
N
Yanagimachi
Ryuzo
R
Wakayama
Teruhiko
T
Shiota
Kunio
K
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D065150:Cellular Reprogramming; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D053652:Nuclear Transfer Techniques; D020411:Oligonucleotide Array Sequence Analysis; D032681:Spectral Karyotyping; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
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