Ever since the creation of induced pluripotent cells (iPSCs) from adult somatic cells by the ectopic expression of defined transcription factors 1, 2, whether iPS cells are equivalent to embryonic stem cells (ESCs) in function and safety aspects has been a major concern regarding their potential applications. Previously, we and others have demonstrated that fully reprogrammed iPSCs were capable of producing full-term mice via the tetraploid complementation method 3,4,5, yet a thorough postnatal development evaluation of iPS mice is still lacking.

We next analyzed the embryos derived from 4n-iPS cells and ES cells by dissecting pregnant mice at embryonic days (E) 13.5, 16.5 and 19.5 (P0), respectively. Although the survival rates of iPSC- and ESC-derived embryos were both very low, slightly higher survival rates were observed among iPSC-derived embryos at all examined time points (Figure 1B). Comparable arrest rates (dominated at E6.5 to E8.5) and same phenotypes between the iPSC- and ESC-derived embryos were observed, including resorbing decidua, resorbed embryo proper with well-formed placenta, and arrested embryos with abdomen closure failure and interstitial bleeding (Supplementary information, Figure S1). After delivery, 17 pups derived from 4N-iPS cells and 12 from ES cells had very low respiration rate and weak breath (Figure 1B), and died within half an hour, most likely due to pulmonary insufficiency caused by respiratory failure (RF). Open eyelid (OE) defect with congenital cataracts was also found among over one-fourth of the total number of iPSC- and ESC-derived pups at P0 (Figure 1B). No difference between the iPS and ES groups was observed in terms of these defects.

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