iPS Cells Remember their Past

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In another twist along the road of cellular reprogramming two leading groups of stem cell scientists in Massachusetts have discovered that induced pluripotent stem (iPS) cells are not as similar to embryonic stem cells as first thought.

iPS cells, first reported in 2006, are made using genetic engineering technologies that cause mature cells (such as a skin cell) to be ‘reprogrammed’ back to a pluripotent stem cell similar in many ways to an embryonic stem cell. Reprogramming technologies are of great interest to scientists as they provide a source of cells for research previously unavailable. For example a researcher wanting to study a degenerative neuronal disease such as Parkinson’s can now make iPS cells from a patient with Parkinson’s and then go on to create neurons from those iPS cells and use them to study the disease in the laboratory.

Prior to the discovery of iPS cells, researchers wanting to work with reprogrammed cells mainly used a technique known as somatic cell nuclear transfer (SCNT). This technique involves the use of an egg to reprogram the adult cell with stem cells then derived from the resulting embryo. Scientists have been able to make embryonic stem cells from SCNT embryos from many different types of animals but never humans.

The two groups, both of whom are associated with the Harvard Stem Cell Institute, this week simultaneously published their results in the journals Nature and Nature Biotechnology concluding that iPS cells retain a memory of their cell of origin which affects their differentiation potential when compared with other pluripotent stem cells.

Working in mice, George Daley and team at Children’s Hospital Boston compared embryonic stem cells from SCNT and iPS cells made from different starting cells. They found that the iPS cells favoured making their tissue of origin whilst the SCNT derived cell behaved more like embryonic stem cells. Also using mice, Konrad Hochedlinger and his group at Harvard University reported similar findings when they compared iPS cells from various starting tissues including muscle, skin, blood and found that the tissues the original cells came from determined the behaviour of the iPS cells. The reason behind these findings seems to be that the reprogramming process to make iPS cells does not fully erase the markers that specify which genes are used by a particular cell.

But what does this all mean for stem cell science? Ultimately findings such as these will help to improve reprogramming technologies. It also means that scientists need to be able to continue to work with and explore all of the different types of stem cells – iPS and embryonic stem cells derived from both donated IVF embryos and SCNT embryos. Limiting research by restricting access to certain cell types at this stage would severely impact progress towards using these cells to understand and ultimately treat disease.

Want to read more? Nature has posted a blog including links to the articles (subscription required) and CIRM have written a blog which you can read here.

The ASCC's Collaborative Stream 2 is dedicated to investigating Reprogramming and Induction of Pluripotency, to read more about its eight research modules click here. 

To learn more about the different types of stem cells you can read our Fact Sheets here.

Journal References

Jose M Polo,Susanna Liu,Maria Eugenia Figueroa,Warakorn Kulalert,Sarah Eminli,Kah Yong Tan,Effie Apostolou,Matthias Stadtfeld,Yushan Li,Toshi Shioda,Sridaran Natesan,Amy J Wagers,Ari Melnick,Todd Evans & Konrad Hochedlinger. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nature Biotechnology, 2010; DOI: 10.1038/nbt.1667

K. Kim,A. Doi,B. Wen,K. Ng,R. Zhao,P. Cahan,J. Kim,M. J. Aryee,H. Ji,L. I. R. Ehrlich,A. Yabuuchi,A. Takeuchi,K. C. Cunniff,H. Hongguang,S. Mckinney-Freeman,O. Naveiras,T. J. Yoon,R. A. Irizarry,N. Jung,J. Seita,J. Hanna,P. Murakami,R. Jaenisch,R. Weissleder,S. H. Orkin,I. L. Weissman,A. P. Feinberg& G. Q. Daley Epigenetic memory in induced pluripotent stem cells. Nature, 2010; DOI: 10.1038/nature09342

 

  • Comments

  • Shi V. Liu
    24/07/2010 12:56:00 AM
    All the evidence so far collected has proved that iPS reprogramming cannot turn ANY cell into ESC-like or equivalent cell(see a series of publications collected at http://im1.biz/iPS.htm). Turning developmental clock back is a dream not a reality.

    All iPSCs are distinct from ESCs because they are just some transformed pre-existing stem cells or other cells identified as "stem" cells. The efficiency as well as the degree of "reprogramming" is ultimately determined by how much the original cells used for reprogramming have already differentiated away from the ESCs. "Complete" "reprogramming" of ANY adult cell back to ESC is just a hype not a reality. No "fully" reprogrammed iPSCs have passed the real test for demonstrating their complete equivalence to ESCs. More dangerously, at least some if not most iPSCs are just incorrectly programmed stem cells or, in other words, man-made cancer stem cells (mmCSCs). Unfortunately, many iPS researchers just cannot remember or, in fact, has intentionally neglected what I have discovered about the true nature of iPSCs and iPS reprogramming.

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