The iPSC-ESC gap

Human cells reprogrammed into multipotent stem cells display fundamental differences from true embryonic stem cells

By | February 2, 2011

Induced pluripotent stem (iPS) cells -- adult cells that have been de-differentiated into an embryonic-like state -- have "hotspots" in their genomes that are not completely reprogrammed, according to a new study in linkurl:Nature.;
Human embryonic stem cells
Nissim Benvenisty, linkurl:Wikimedia Commons;
The research demonstrates that iPS cells are fundamentally different from embryonic stem (ES) cells, and will require more analysis prior to use in therapies and disease models. "The results indicate once again that we still have so much to learn about this fascinating process of reprogramming," said linkurl:George Daley; of Harvard Medical School and Children's Hospital Boston, who was not involved in the research, in an email to The Scientist. "While iPS cells are remarkably similar to ES cells, this study points out important differences, and gives us an ever more refined view of the nature of iPS cells." After producing the first genome-wide methylation maps of human ES cells and somatic cells in 2009, linkurl:Joseph Ecker; and colleagues at the Salk Institute turned their sights on mapping methylation -- the addition of methyl groups to DNA, which can affect gene expression -- in iPS cells. The team generated whole-genome DNA methylation profiles, at a single-base resolution, for 11 cell lines, including iPS cells derived using a range of technologies, ES cells, differentiated iPS and ES cells, and parent cell lines: fibroblasts, adipose cells, and embryonic lung cells. Notably, the team mapped not just CG methylation, the standard type of methylation analyzed in most studies, but also non-CG methylation, which Ecker previously showed makes up 25 percent of the methylation in ES cells but is rarely present in somatic cells. The iPS and ES cells shared global patterns of methylation, but as the team zoomed in for a closer look, the differences were striking. They identified 1,175 regions in iPS cells with different methylation patterns than ES cells, including 22 large regions, or "hotspots," where iPS cells lacked the non-CG methylation characteristic of ES cells. The somatic cells from which the iPS cells were derived also lack these non-CG methylation zones, suggesting that iPS cells fail to acquire these changes as they are de-differentiated into a stem cell-like state. Additionally, the researchers found that iPS cell hotspots were retained after re-differentiation into various cell types, which could have consequences for cells derived from iPS cells, the authors noted. The findings complement linkurl:two studies published last year; -- one by Daley's lab and another by linkurl:Konrad Hochedlinger; and colleagues at Harvard -- that found that mouse iPS cells retain an "epigenetic memory" of the cell type from which they were derived, a footprint that can affect the cells' ability to develop into different lineages. The results in no way decrease the importance of iPS technology, emphasized Ecker. "iPS is a really powerful technology," he said, and the hotspots can hopefully be used as diagnostic markers for scientists to evaluate iPS cells. "We need to know whether those cells are being reprogrammed properly, and this provides an assay," he said. Ecker, J.R. et al., "Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells," Nature, doi:10.1038/nature09798.
**__Related stories:__***linkurl:iPSCs less pliable than ESCs?;
[19th July 2010] *linkurl:Pluripotency not required;
[27th January 2010] *linkurl:How to ID human pluripotency;
[11th October 2009]


Avatar of: Mike Waldrep

Mike Waldrep

Posts: 155

February 2, 2011

Interesting! I hope that everyone is having a happy Groundhog Day! I'm sorry that I didn't say anything about it yesterday,but it slipped my mind!
Avatar of: don margolis

don margolis

Posts: 3

February 2, 2011

Thousands of serious articles about ESC and iPSC as if either will ever help a human being who is sick today. Notice that EVERY published article is so positive and completely ignores the major negatives.\n\nNo matter how many awards you publicists give Thomson and his Japanese colleague, THEY WERE WRONG about iPSC. This writer never mentions (fear of being whacked out by PhRMA?) that EVERY study shows that ESC tumours also occur with iPSC. They never mention the major problem of immune rejection. They never mention that ESC and iPSC cost ten times as much as ASC. Only the ESC/iPSC science-fiction is allowed in the worst medical system the world has ever seen, soon to be even worse under ObamaCare.\n\nYou are perhaps fooled by the corrupt headlines of ISSCR stating that "Adult Stem Cells cause Cancer" at the top of decent scientific articles about iPSC and its tumours. \n \nSo do as they all do, kiss PhRMA's derriere because that is where the money is, and ignore the truths about ESC and ASC. Chirp about one fraudulent ESC "trial" while ignoring that ASC are 15 years ahead in SCI research, even assuming that ONE-PATIENT trial is successful. (It can't be.)\nDon Margolis, Chairman\nRepair Stem Cell Institute\n
Avatar of: Shi Liu

Shi Liu

Posts: 32

February 2, 2011

Finally, Nature('s publication) admitted the "gap" between iPSC and ESC. But had I already told Nature such truth years ago? How many of my submissions to Nature (and also other "top" journals) were rejected by Nature (and also other "top" journals)? How many iPSC researchers have (collectively and intentionally) ignored my PUBLICATIONS criticizing their iPS hyping. Actually I have PUBLISHED a lot of "anti-iPS" articles addressing the flaws in iPS research (they can be viewed at ) and most leading iPS researchers should know me because I have sent to them my criticisms before and after their PUBLICATION. As a matter of fact, Yamanaka "thanked" me in Science in 2008 after he realized that my discovery of his "cancer-free" iPSCs as cancer cells is very correct as evidenced by his later (RE)-discovery of the cancer risk in his "safe" iPSCs.\nLet me repeat MY DISCOVERY on iPSCs: incorrectly programmed stem cells or, in other words, man-made cancer stem cells. They should never be equaled to ESCs, not matter how "indistinguishable" (really) they are to ESCs by some experts' view.\nBy the way, if people wish to use iPSCs as surrogate cancer cells for screening anti-cancer drugs, please contact me because I have filed a patent on it.\n

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