New ways of inducing pluripotency and additional applications for the CRISPR-Cas system

The CRISPR-Cas system for genome editing was launched in 2013 for applications in animal transgenesis and continues advancing in 2014
The CRISPR-Cas system for genome editing was launched in 2013 for applications in animal transgenesis and continues advancing in 2014

The first weeks of 2014 have generated interesting technical advances in animal transgenesis, and prestigious ISTT members have been involved in them. If this is just a sample of what will come next it would seem appropriate to call this starting 2014 year the wonder year. This past week we knew about a new manner for inducing pluripotency, simply exposing somatic cells to a low pH, using a physical stimulus, transiently applied during a short period of time. This acidic exposure appears to trigger the reprogramming steps required to convert somatic into fully capable pluripotent cells, sustenting the generation of germ-line transmitting chimeras. Furthermore, these STAP (Stimulus-Triggered Acquisition of Pluripotency) cells appear to be able to contribute to both the embryonic and extra-embryonic lineages, thus constituting a unique status of pluripotency. These awesome two papers, by Haruko Obokata and collaborators, have been published in Nature, and include as co-author in one and senior corresponding author in the other, ISTT member Teruhiko Wakayama, the first scientist awarded the ISTT Prize.

Also last week we learnt about the first non-human knockout primates. A group of Chinese scientists (Yuyu Niu and collaborators), including the most prestigious centres involved in the generation of animal models in China, published a paper in Cell where they reported a new application for the powerful and novel CRISPR-Cas technology to produce mutant monkeys. They generated, for the first time, twin cynomolgus monkeys (Macaca fascicularis) with two targeted loci, Ppar-g and Rag1, in one single step. This collaborative work included as co-authors ISTT member and ISTT Prize awarded scientist Qi Zhou, as well as Xiaoyang Zhao, who received the first ISTT Young Investigator Award. This achievement, which was not possible to date with standard technologies, illustrates the unlimited power of the CRISPR-Cas system.

We first learnt about the CRISPR-Cas system, as the responsible for adaptative bacterial immunity, in mid 2012. But it was not until last year, 2013, when the molecular reagents become amenable and applicable for genome editing in animal cells and embryos, for the generation of a variety of genetically-modified animals, including all sorts of transgenic and mutant types, with an explosion of papers and applications. Today, 1st February 2014, as many as 88 papers appear listed in PubMed combining “CRISPR genome editing”. The amazing simplicity of this sytem, and the ease by which anyone can start using this technology in the lab, simply obtaining the two required plasmids (carrying the RNA guide, where the target homologous sequence must be engineered, and the Cas9 nuclease) from diverse providers, including Addgene, explains why the CRIRPR-Cas technology is now being considered a true revolution in our field, in animal transgenesis.

1 thought on “New ways of inducing pluripotency and additional applications for the CRISPR-Cas system”

  1. The STAP cells are currenty under investigation at RIKEN in Japan and by the Nature journal, which published these impressive papers, due a number of concerns that have been raised after the publication of these experiments. Various experienced stem-cell labs have failed so far to reproduce the results as reported in the mentioned articles. In addition, some figures included in the publications might be associated with duplicated or alteration issues. The authors are currently reviewing all these allegations, in collaboration with their institutions and the scientific journal, but remain confidents in their findings and about the validity of the published results. A final response is expected soon and will be disseminated. In the meantime, additional information can be obtained from various sources, including:
    http://www.nature.com/news/acid-bath-stem-cell-study-under-investigation-1.14738
    http://www.ipscell.com/
    http://news.sciencemag.org/health/2014/02/high-profile-stem-cell-papers-under-fire
    http://phys.org/news/2014-02-image-anomalies-shadow-acid-bath-stem-cell.html
    http://www.bostonglobe.com/news/nation/2014/02/19/papers-reporting-new-stem-cell-technique-being-investigated/R6Z48wWsKQSHoG4R8Nk74K/story.html

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