Editing Transdifferentiation (section)

=== Lineage-instructive approach ===

In this approach, [[transcription factor]]s from [[progenitor cell]]s of the target cell type are [[transfection|transfected]] into a somatic cell to induce transdifferentiation.<ref name="Forcing cells to change lineages"/> There exists two different means of determining which transcription factors to use: by starting with a large pool and narrowing down factors one by one<ref name="ReferenceB">{{Cite journal 
| last1 = Ieda | first1 = M. 
| last2 = Fu | first2 = J. D. 
| last3 = Delgado-Olguin | first3 = P. 
| last4 = Vedantham | first4 = V. 
| last5 = Hayashi | first5 = Y. 
| last6 = Bruneau | first6 = B. G. 
| last7 = Srivastava | first7 = D. 
| doi = 10.1016/j.cell.2010.07.002 
| title = Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors 
| journal = Cell 
| volume = 142 
| issue = 3 
| pages = 375–386 
| year = 2010 
| pmid = 20691899 
| pmc =2919844 
}}</ref> or by starting with one or two and adding more.<ref>{{Cite journal 
| last1 = Vierbuchen | first1 = T. 
| last2 = Ostermeier | first2 = A. 
| last3 = Pang | first3 = Z. P. 
| last4 = Kokubu | first4 = Y. 
| last5 = Südhof | first5 = T. C. 
| last6 = Wernig | first6 = M. 
| doi = 10.1038/nature08797 
| title = Direct conversion of fibroblasts to functional neurons by defined factors 
| journal = Nature 
| volume = 463 
| issue = 7284 
| pages = 1035–1041 
| year = 2010 
| pmid = 20107439 
| pmc =2829121 
| bibcode = 2010Natur.463.1035V 
}}</ref> One theory to explain the exact specifics is that [[ectopia (medicine)|ectopic]] Transcriptional factors direct the cell to an earlier progenitor state and then redirects it towards a new cell type. Rearrangement of the [[chromatin]] structure via [[DNA methylation]] or [[histone]] modification may play a role as well.<ref>{{Cite journal 
| last1 = Ang | first1 = Y. S. 
| last2 = Gaspar-Maia | first2 = A. 
| last3 = Lemischka | first3 = I. R. 
| last4 = Bernstein | first4 = E. 
| title = Stem cells and reprogramming: Breaking the epigenetic barrier? 
| doi = 10.1016/j.tips.2011.03.002 
| journal = Trends in Pharmacological Sciences 
| volume = 32 
| issue = 7 
| pages = 394–401 
| year = 2011 
| pmid = 21621281 
| pmc =3128683 
}}</ref> Here is a list of in vitro examples and [[Examples of in vivo transdifferentiation by lineage-instructive approach|in vivo examples]]. [[In vivo]] methods of transfecting specific mouse cells utilize the same kinds of vectors as [[in vitro]] experiments, except that the vector is injected into a specific organ. Zhou et al. (2008) injected Ngn3, Pdx1 and Mafa into the dorsal splenic lobe (pancreas) of mice to reprogram pancreatic [[exocrine]] cells into β-cells in order to ameliorate hyperglycaemia.<ref>{{Cite journal 
| last1 = Zhou | first1 = Q. 
| last2 = Brown | first2 = J. 
| last3 = Kanarek | first3 = A. 
| last4 = Rajagopal | first4 = J. 
| last5 = Melton | first5 = D. A. 
| title = In vivo reprogramming of adult pancreatic exocrine cells to β-cells 
| doi = 10.1038/nature07314 
| journal = Nature 
| volume = 455 
| issue = 7213 
| pages = 627–632 
| year = 2008 
| pmid = 18754011 
| pmc = 9011918 
| bibcode = 2008Natur.455..627Z 
| s2cid = 205214877 
}}</ref>