Editing Transdifferentiation (section)

==Induced and therapeutic examples==

The first example of functional transdifferentiation has been provided by Ferber et al.<ref>Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N, Karasik A (2000) Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. http://www.nature.com/nm/journal/v6/n5/full/nm0500_568.html</ref> by inducing a shift in the developmental fate of cells in the liver and converting them into '[[Pancreas|pancreatic]] [[Beta cell|beta-cell]]-like' cells. The cells induced a wide, functional and long-lasting transdifferentiation process that reduced the effects of [[hyperglycemia]] in diabetic mice.<ref name="nature.com">Sarah Ferber, Amir Halkin, Hofit Cohen, Idit Ber, Yulia Einav, Iris Goldberg, Iris Barshack, Rhona Seijffers, Juri Kopolovic, Nurit Kaiser & Avraham Karasik (2000) - "[http://www.nature.com/nm/journal/v6/n5/full/nm0500_568.html Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia]"</ref> Moreover, the trans-differentiated beta-like cells were found to be resistant to the [[autoimmune]] attack that characterizes [[type 1 diabetes]].<ref>Shternhall-Ron K et al., Ectopic PDX-1 expression in liver ameliorates type 1 diabetes, Journal of Autoimmunity (2007),
doi:10.1016/j.jaut.2007.02.010. http://www.orgenesis.com/uploads/default/files/shternhall-jai-2007.pdf</ref>

The second step was to undergo transdifferentiation in human specimens. By transducing liver cells with a single gene, Sapir et al. were able to induce human liver cells to transdifferentiate into human beta cells.<ref name="pnas.org">Tamar Sapir, Keren Shternhall, Irit Meivar-Levy, Tamar Blumenfeld, Hamutal Cohen, Ehud Skutelsky, Smadar Eventov-Friedman, Iris Barshack, Iris Goldberg, Sarah Pri-Chen, Lya Ben-Dor, Sylvie Polak-Charcon, Avraham Karasik, Ilan Shimon, Eytan Mor, and Sarah Ferber (2005) [http://www.pnas.org/content/102/22/7964 Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells]</ref>

This approach has been demonstrated in mice, rat, [[xenopus]] and human tissues.<ref name="Al-Hasani">{{cite journal | last1 = Al-Hasani | first1 = K | last2 = Pfeifer | first2 = A | last3 = Courtney | first3 = M | last4 = Ben-Othman | first4 = N | last5 = Gjernes | first5 = E | last6 = Vieira | first6 = A | last7 = Druelle | first7 = N | last8 = Avolio | first8 = F | last9 = Ravassard | first9 = P | last10 = Leuckx | first10 = G | last11 = Lacas-Gervais | first11 = S | last12 = Ambrosetti | first12 = D | last13 = Benizri | first13 = E | last14 = Hecksher-Sorensen | first14 = J | last15 = Gounon | first15 = P | last16 = Ferrer | first16 = J | last17 = Gradwohl | first17 = G | last18 = Heimberg | first18 = H | last19 = Mansouri | first19 = A | last20 = Collombat | first20 = P | year = 2013 | title = Adult Duct-Lining Cells Can Reprogram into β-like Cells Able to Counter Repeated Cycles of Toxin-Induced Diabetes | journal = Dev. Cell | volume = 26 | issue = 1| pages = 86–100 | doi = 10.1016/j.devcel.2013.05.018 | pmid = 23810513 | doi-access = free | hdl = 11858/00-001M-0000-0014-3C2F-6 | hdl-access = free }}</ref>

Schematic model of the [[hepatocyte]]-to-beta cell transdifferentiation process. Hepatocytes are obtained by liver biopsy from diabetic patient, cultured and expanded [[ex vivo]], transduced with a [[PDX1]] virus, transdifferentiated into functional [[insulin]]-producing beta cells, and transplanted back into the patient.<ref name="pnas.org"/>

[[Granulosa cell|Granulosa]] and [[Theca of follicle|theca cells]] in the [[Ovary|ovaries]] of adult female mice can transdifferentiate to [[Sertoli cell|Sertoli]] and [[Leydig cell]]s via induced knockout of the [[Forkhead box L2|FOXL2]] gene.<ref name="pmid20005806">{{cite journal | vauthors = Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schütz G, Cooney AJ, Lovell-Badge R, Treier M | display-authors = 6 | title = Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation | journal = Cell | volume = 139 | issue = 6 | pages = 1130–42 | date = December 2009 | pmid = 20005806 | doi = 10.1016/j.cell.2009.11.021 | doi-access = free }}</ref> Similarly, Sertoli cells in the [[Testicle|testes]] of adult male mice can transdifferentiate to granulosa cells via induced knockout of the [[DMRT1]] gene.<ref name="pmid21775990">{{cite journal | vauthors = Matson CK, Murphy MW, Sarver AL, Griswold MD, Bardwell VJ, Zarkower D | title = DMRT1 prevents female reprogramming in the postnatal mammalian testis. | journal = Nature| volume = 476| issue = 7358| pages = 101–4|date=July 2011 | pmid = 21775990| doi = 10.1038/nature10239 | pmc = 3150961 }}</ref>