http://bit.ly/29Tjk0vJacob H. Hanna2016 Jul 14 1:49 p.m. (9 hours ago)
Theunissen et al. Cell Stem Cell 2014 reported failure to detect human naive PSC derived cell integration in chimeric mouse embryos obtained following microinjection into mouse blastocysts, as was reported for the first time by our group (Gafni et al. Nature 2013). However, the authors failed to discuss that among different caveats, imaging and cell detection methods applied by Theunissen et al. Cell Stem Cell 2014 were (and still) not at par with those applied by Gafni et al. Nature 2013.
Regardless, we find it important to alert the authors and readers that Theunissen and Jaenisch have now revised (de facto, retracted) their previous negative results, and are able to detect naïve human PSC derived cells in mouse embryos at more than 0.5% of embryos obtained (Theunissen et al. Cell Stem Cell 2016) <
http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30161-8 >. While the authors of the latter recent invest great effort to downplay the significance of their new findings and avoid conducting advanced imaging and/or histology sectioning on such obtained embryos, we find the 0.5% reported efficiency is remarkable considering that the 5i/LA naive human cells used lack epigenetic imprinting (due to aberrant loss of DNMT1 protein that is not seen in mouse naive ESCs!!
) and are chromosomally abnormal. The latter features are well known inhibitors for chimera formation even when attempting to conduct same species chimera assay with mouse naive PSCs.
Finally, and less importantly, a copy of a previous version submitted and rejected by Cell journal earlier this year (kindly provided to us by a co-author), the authors present an exact same copy of their Figure 7, except that in the older rejected version also NHSM conditions yielded an embryo with detectable human cell integration. Despite of our open efforts, unfortunately the authors and the journal did not provide us with original raw data to exclude selective omission or biased manipulation of data <
>. As such we question the integrity, objectivity and quality of the data being presented relating to this discussion by this group of authors.