Published on September 27, 2015
1. Dedifferentiation Presented by Hang Jie Justin Izz Hariz Por Kwang Jeff Zoe
2. Introduction O Dedifferentiation is an important biological phenomenon: Cells regress from a specialized function to a simpler state reminiscent of stem cells O Stem cells that are derived by dedifferentiation could be a new resource for regenerative medicine (poses no risk of genetic incompatibility or immune rejection) O It also offers an ethically acceptable alternative route to obtain an abundant source of stem cells compare than the use of stem cells derived from embryonic tissue - (CAI et al. 2007)
3. How to reprogram stem cells? O Experimented by - Takahashi and Yamanaka O Introduce four genes (Oct-3/4, Sox2, c-Myc, and KLF4) into an adult mouse fibroblast population O Generate colonies with the characteristics of ESCs O Colonies were capable of differentiation to endodermal, ectodermal, and mesodermal lineages after transplant in immunodeficient mice - (Friedmann-Morvinski & Verma 2014)
4. - (EuroStemCell 2012)
5. Phenomenon of Dedifferentiation O The phenomenon can be observed at the level of : O Genetic - cell undergoes reversion to progenitor cell gene expression profile O Protein - evidenced by the up-regulation of progenitor & down-regulation of differentiated cell related proteins O Morphology - dedifferentiated cells are smaller, fewer organelles and have high karyoplasmic ratio O Functional - cells regains the capacity to proliferate - (CAI et al. 2007)
6. Medical Application & Research 1. To study neurological diseases O Obtain the neurons from patient through dedifferentiation of their skin cells and reprogram them into affected neurons O Thus able to further work on the affected neurons by searching and testing new drugs to treat or protect patients against the disease - (EuroStemCell 2012)
7. 2. Dedifferentiation of epithelial cells for corneal maintenance: O Stem cells in corneal limbus forming a ring of tissue around the central cornea, and epithelial cells in the central areas O After proliferating, stem cells differentiate into terminal corneal epithelial cells that replace the cells shed in the central cornea - (Yoon et al. 2014)
8. 3. Treatment of Osteoarthritis O Technique developed by - Dr Paul Genever O To revitalize cells from older people with osteoarthritis to repair worn or damaged cartilage, therefore reducing pain O Cultivated spheroid clusters of cells in tiny cavities, by using pharmaceutical to induce cell-self-eating effects and consequently reduce in size, which stimulate dedifferentiation and the cells revert to embryonic state - (Alexandra Thompson 2015)
9. Current Medical development -Clinical Stages O Masayo Takahashi, has been using induced pluripotent stem (iPS) cells to prepare a treatment for age-related macular degeneration. O Skin cells taken from people with the disease and converted them to iPS cells. O Coax these cells to become retinal pigment epithelium cells, and then to grow into thin sheets that can be transplanted to the damaged retina. - (Cyranoski 2014)
10. Safety test O Researches has been done on iPS cells in monkey and there is no immune reaction found. O There have been concerns that iPS cells could cause tumours, but Takahashi's team has found that to be unlikely in mice and monkeys. - (Cyranoski 2014)
11. Future Application O Cartilage injury remains a challenge in orthopedic surgery due to the fact that articular cartilage has limited capacity for intrinsic healing. O The main cells in the cartilage are the chondrocytes. When they dedifferentiate, the tend to lose their bone like characteristics. O To generate more chondrocytes for studies, there will have to be a dedifferentiation of chondrocytes. - (Wei et al. 2012)
12. Future Application O Therefore through the dediffrentiation of chondrocytes, studies on redifferentiation of chondrocytes can be carried out. O Successful redifferentiation of chondrocytes can be used in replacing the dedifferentiated chondrocytes in the bones to improve the rate of cartilage healing. - (Lin et al. 2008)
13. Limitation in Dedifferentiation Process O High medical cost O Lack of large-scale culture technologies O Longer timeframe needed to prepare the cells for transplantation (eg: crucial spinal cord injuries) O Impractical to isolate neurons directly from a patient’s brain O Cells isolated from the patient will be affected and have a little therapeutic value
14. O Low quality of cells which derived from somatic cells of aged individuals (incidence of spontaneously occurring tumors) O Integration site of retroviral vectors and also the use of undefined serum-containing media to support IPSC generation will increase the risk of insertional mutagenesis and the risk of tumorigenicity O The use of oncogenic transgenes, such as MYC gene (code for transcription factor), can also increase the risk of tumour development Limitation in Dedifferentiation Process
15. Conclusion O Cell dedifferentiation is an important part of the life of a cell and is an important part of medical research O More research towards the dedifferentiation of cells are needed to be carried out to ensure that the dedifferentiation pathways are fully understood
16. References O Alexandra Thompson 2015, Researchers develop dedifferentiation technique to help treat osteoarthritis, viewed on 26th September 2015, <https://www.regmednet.com/users/1034-alexandra- thompson/posts/2947-researchers-develop-dedifferentiation-technique- to-help-treat-osteoarthritis#> O CAI, S., FU, X. & SHENG, Z., 2007. Dedifferentiation: A New Approach in Stem Cell Research. BioScience, 57(8), p.655, viewed on 26th September 2015, <http://bioscience.oxfordjournals.org/content/57/8/655> O Cyranoski, D 2014, Next-generation stem cells cleared for human trial, Nature, viewed on 26th September 2015, <http://www.nature.com/news/next-generation-stem-cells-cleared-for- human-trial-1.15897> O EuroStemCell 2012, IPS cells and reprogramming: turn any cell of the body into a stem cell, viewed on 26th September 2015, <http://www.eurostemcell.org/factsheet/ips-cells-and-reprogramming- turn-any-cell-body-stem-cell> O Friedmann-Morvinski, D. & Verma, I.M., 2014. Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO reports, 15(3), pp.244–53, viewed on 26th Semptember 2015, <http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3989690&to ol=pmcentrez&rendertype=abstract>
17. O Lin, Z. et al., 2008. Gene expression profiles of human chondrocytes during passaged monolayer cultivation. Journal of Orthopaedic Research, 26(9), pp.1230–1237 O Wei, Y. et al., 2012. Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix. European cells & materials, 23, pp.1–12, viewed on 26th September 2015, <http://www.ncbi.nlm.nih.gov/pubmed/22241609> O Yoon, J.J., Ismail, S. & Sherwin, T., 2014. Limbal stem cells: Central concepts of corneal epithelial homeostasis. World journal of stem cells, 6(4), pp.391–403, viewed on 26th September 2015, <http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid= 4172668&tool=pmcentrez&rendertype=abstract> References
18. Thank You
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