Epigenetic Memory in Induced Pluripotent Stem Cells (Summary of an Actual Journal in Nature)

               

                 In our body, there are billions of cells but in genetics, stem cells are the type of cells that we focus on.  There are many controversies over the use of stem cells such as the use of embryonic stem cells in medical research and treatment.  Embryonic stem cells are important in many researches because of its pluripotent property or the ability to become any type of cells but that comes with a cost.  They can only be obtained from actual embryos.  Therefore, induced pluripotent stem cells (iPSCs) are thought to be the answer to this problem. 

                

               iPSCs are not actually embryonic stem cells so that means that an actual embryo or going to b e human cell is not required to be destroyed.  However, they have the same property which is being able to specialize into any cells.  iPSCs are made by using two techniques, nuclear transfer and transcription based reprogramming, to turn somatic adult cells back into the pluripotent stem cells.  Although not having to destroy embryos and being able to differentiate into any cells ignoring the original cells sounds as a sound solution to the problem with embryonic stem cells, this study published in Nature in the year 2010 has proven that there are still some problems.

               “Epigenetic memory” is discovered in the iPSCs by this research [1] .  Epigenetic memory is when the iPSCs that are supposed to be reprogram and reset into pluripotent stem cells show similar properties to that of the somatic cells origin.  The DNA has methylation and when the adult cell is reprogramed, that methylation still leaves its traces on the iPSCs.  The iPSCs obtained from original cells are supposed to be able to differentiate into different type of cells that are needed but when done, they show different properties.  iPSCs with original cells similar to the wanted cells will have better properties of it.  For example, iPSCs from blood cell will have more of the adult blood cells properties when differentiated than iPSCs from muscle cell.  As said by Dr. George Daley in abc news, “It's an advantage when you want to make the same tissue type, but not if you're looking at making something new. [4] ”

                 Epigenetic memory is tested using the comparison of hematopoietic (the production of all types of blood cells [5] ) stem cells from the fertilized embryos (fESCs), nuclear transfer embryonic stem cells (ntESCs), and iPSCs.  These stem cells are taken from mice and then reprogrammed to get the stem cells.  They all show the hematopoietic properties but at different levels of effectiveness.  “Blood derived iPSCs” are found to have more hematopoietic cells than “fibroblast iPSCs”.  Also from the study, ntESCs form more hematopoietic cells than fESCs.  This result shows that iPSCs has epigenetic memory and will have epigenetic marks from the original cell which will be good to differentiation into cells of similar specialization and for this case, into hematopoietic cell. 

                     Next, the researchers study into the DNA methylation of the stem cells.  Differentially methylated regions (DMR) or a special gene with methylation are compared between ntESCs, blood derived iPSCs, fibroblast derived iPSCs, and fESCs.  The comparison is done by a technique called comprehensive high-throughput array-based relative methylation.  From the CHARM done to compare DMR of different stem cells, it shows that ntESCs are the most similar fESCs meaning that nuclear transfer is a more efficient way or reprogramming.  Higher blood forming potential is also seen in blood derived iPSCs than in fibroblast derived iPSCs. 

                After that, the researchers are thinking up a way to reset the differentiation of the differentiated cells to make it have a better blood forming potential.  This is done by having a tertiary reprogramming done on a cell.  So for this instance, a non-blood cell is reprogrammed into an iPSCs.  Then it is differentiated into a blood forming cell but it has low blood forming potential from the epigenetic memory.  Nonetheless, that cell is undergone tertiary reprogramming to become iPSCs once more but this time, it has a higher blood forming potential.  Another way to increase the blood forming potential of the cell is to do a drug treatment involving “chromatin modifying compound” [1] also increase blood forming potential.

                From other sources such as abc news, this research is a topic of argument.  "If you make an IPS cell from skin cells and you want to use that for studying blood diseases, then we know now that you might be better off starting with blood tissue instead," argued Ihor Lemischka. [4]  Nonetheless, all researchers agree upon the fact that this will without a doubt have potential in the future if more research has been done.  Sean Morrison pointed out “In the end, adult stem cells will probably prove superior for certain therapeutic applications, reprogrammed cells might work for other applications, and embryonic cells for others.” [4]

                As more recent research has been done, more information about the iPSCs is discovered.  In a recent research, iPSCs are found to be very similar to embryonic stem cells but only when the cells are in the early fetal stage.  “This finding may lead to exciting new ways to study early human development, but it also may present a challenge for transplantation, because the cells you end up with are not something that's indicative of a cell you'd find in an adult or even in a newborn baby," said William Lowry.  [3] In another research, iPSCs shows a good chance of differentiating into the same endoderm cells with a lot of overlap in the genes.  The researchers therefore conclude that iPSCs can be used for therapies involving the endoderm cells [2] .

                With more researches into induced pluripotent stem cells, the world is likely to become a better place with lots of diseases cured without the killing of what is going to become human.

Bibliography

1. 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." Epigenetic memory in induced pluripotent stem cells. 467.16 (2010): 285-90. Print.
2. ScienceDaily, . "Cells Derived from Different Stem Cells: Same or Different?." Cells Derived from Different Stem Cells: Same or Different? 02 May 2011, n. pag. Web. 30 Apr. 2012. http://www.sciencedaily.com/releases/2011/05/110502121749.htm.
3. ScienceDaily, . "Cells Derived from Pluripotent Stem Cells Are Developmentally Immature." Cells Derived from Pluripotent Stem Cells Are Developmentally Immature 17 Aug 2011, n. pag. Web. 30 Apr. 2012. http://www.sciencedaily.com/releases/2011/08/110817092227.htm.
4. Salahi, Lara. "Reprogrammed Adult Cells Not an Alternative to Embryonic Stem Cells." Reprogrammed Adult Cells Not an Alternative to Embryonic Stem Cells 20 Jul 2010, n. pag. Web. 30 Apr. 2012. http://abcnews.go.com/Health/Wellness/reprogrammed-adult-cells-retain-memory/story?id=11201017.
5. "Definition of Hematopoiesis." MedicineNet.com. MedicineNet, Inc., 19 Mar 2012. Web. 30 Apr 2012. http://www.medterms.com/script/main/art.asp?articlekey=19775.
6. "Image Glossary > Cellular Reprogramming." STEM CELL SCHOOL. Genetics Policy Institute, n.d. Web. 30 Apr 2012. http://www.stemcellschool.org/ig-cellular-reprogramming.html.