Examples of in vitro transdifferentiation by lineage-instructive approach

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A list [1] [2] [3] [4] of examples of transdifferentiation:

See also

Related Research Articles

Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis.

<span class="mw-page-title-main">Oct-4</span> Mammalian protein found in Homo sapiens

Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.

In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.

<span class="mw-page-title-main">FGF3</span> Protein-coding gene in humans

INT-2 proto-oncogene protein also known as FGF-3 is a protein that in humans is encoded by the FGF3 gene.

<span class="mw-page-title-main">Glial cell line-derived neurotrophic factor</span> Protein-coding gene in the species Homo sapiens

Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. It is also responsible for the determination of spermatogonia into primary spermatocytes, i.e. it is received by RET proto-oncogene (RET) and by forming gradient with SCF it divides the spermatogonia into two cells. As the result there is retention of spermatogonia and formation of spermatocyte.

<span class="mw-page-title-main">Macrophage migration inhibitory factor</span> Protein-coding gene in the species Homo sapiens

Macrophage migration inhibitory factor (MIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene. MIF is an important regulator of innate immunity. The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT). CD74 is a surface receptor for MIF.

<span class="mw-page-title-main">Nuclear receptor 4A2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor 4A2 (NR4A2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene. NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.

<span class="mw-page-title-main">Induced pluripotent stem cell</span> Pluripotent stem cell generated directly from a somatic cell

Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."

<span class="mw-page-title-main">KLF4</span> Protein-coding gene in the species Homo sapiens

Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).

<span class="mw-page-title-main">SYT1</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.

<span class="mw-page-title-main">ASCL1</span> Protein-coding gene in humans

Achaete-scute homolog 1 is a protein that in humans is encoded by the ASCL1 gene. Because it was discovered subsequent to studies on its homolog in Drosophila, the Achaete-scute complex, it was originally named MASH-1 for mammalian achaete scute homolog-1.

Neurogenins, often abbreviated as Ngn, are a family of bHLH transcription factors involved in specifying neuronal differentiation. The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.

<span class="mw-page-title-main">Cell potency</span> Ability of a cell to differentiate into other cell types

Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.

A list of examples of in vivo transdifferentiation through transfection:

List:

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

<span class="mw-page-title-main">GLIS1</span> Protein-coding gene

Glis1 is gene encoding a Krüppel-like protein of the same name whose locus is found on Chromosome 1p32.3. The gene is enriched in unfertilised eggs and embryos at the one cell stage and it can be used to promote direct reprogramming of somatic cells to induced pluripotent stem cells, also known as iPS cells. Glis1 is a highly promiscuous transcription factor, regulating the expression of numerous genes, either positively or negatively. In organisms, Glis1 does not appear to have any directly important functions. Mice whose Glis1 gene has been removed have no noticeable change to their phenotype.

<span class="mw-page-title-main">Tumor microenvironment</span> Surroundings of tumors including nearby cells and blood vessels

The tumor microenvironment (TME) is a complex ecosystem surrounding a tumor, composed of a variety of non-cancerous cells including blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). Mutual interaction between cancer cells and the different components of the TME support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

Tissue nanotransfection (TNT) is an electroporation-based technique capable of gene and drug cargo delivery or transfection at the nanoscale. Furthermore, TNT is a scaffold-less tissue engineering (TE) technique that can be considered cell-only or tissue inducing depending on cellular or tissue level applications. The transfection method makes use of nanochannels to deliver cargo to tissues topically. 

Kristin K. Baldwin is an American scientist who is a professor at the Department of Genetics and Development at Columbia University. Her research focuses on using reprogrammed and induced pluripotent stem cells to identify mechanisms and therapies related to human genetic risk for neurologic and cardiovascular disease. Her lab also studies how disease and aging affect the genome; they have used cloning to produce the first complete genome sequence of a single neuron and helped assess the effect of aging on induced pluripotent stem cells that may be used for cell therapies. They also design bespoke neuronal cells in a dish to understand brain function and disease. Baldwin's earlier work included being the first to clone a mouse from a neuron and being one of three groups to first produce an entire mouse from a skin cell by generating induced pluripotent stem cells. epigenetic changes of the genome and the brain.

References

  1. ↑ Pournasr, B.; Khaloughi, K.; Salekdeh, G. H.; Totonchi, M.; Shahbazi, E.; Baharvand, H. (2011). "Concise Review: Alchemy of Biology: Generating Desired Cell Types from Abundant and Accessible Cells". Stem Cells. 29 (12): 1933–1941. doi: 10.1002/stem.760 . PMID   21997905.
  2. ↑ Vierbuchen, T.; Ostermeier, A.; Pang, Z. P.; Kokubu, Y.; Südhof, T. C.; Wernig, M. (2010). "Direct conversion of fibroblasts to functional neurons by defined factors". Nature. 463 (7284): 1035–1041. doi:10.1038/nature08797. PMC   2829121 . PMID   20107439.
  3. ↑ Adler, A. F.; Grigsby, C. L.; Kulangara, K.; Wang, H.; Yasuda, R.; Leong, K. W. (2012). "Nonviral Direct Conversion of Primary Mouse Embryonic Fibroblasts to Neuronal Cells". Molecular Therapy: Nucleic Acids. 1 (7): e32–. doi:10.1038/mtna.2012.25. PMC   3411320 . PMID   23344148.
  4. ↑ Addis, R. C.; Hsu, F. C.; Wright, R. L.; Dichter, M. A.; Coulter, D. A.; Gearhart, J. D. (2011). Muotri, Alysson Renato (ed.). "Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector". PLOS ONE. 6 (12): e28719. doi: 10.1371/journal.pone.0028719 . PMC   3235158 . PMID   22174877.
  5. ↑ Davis, R. L.; Weintraub, H.; Lassar, A. B. (1987). "Expression of a single transfected cDNA converts fibroblasts to myoblasts". Cell. 51 (6): 987–1000. doi:10.1016/0092-8674(87)90585-x. PMID   3690668. S2CID   37741454.
  6. ↑ Tachibana, M.; Takeda, K.; Nobukuni, Y.; Urabe, K.; Long, J. E.; Meyers, K. A.; Aaronson, S. A.; Miki, T. (1996). "Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics". Nature Genetics. 14 (1): 50–54. doi:10.1038/ng0996-50. PMID   8782819. S2CID   205342756.
  7. ↑ Heins, N.; Malatesta, P.; Cecconi, F.; Nakafuku, M.; Tucker, K. L.; Hack, M. A.; Chapouton, P.; Barde, Y. A.; Götz, M. (2002). "Glial cells generate neurons: The role of the transcription factor Pax6". Nature Neuroscience. 5 (4): 308–315. doi:10.1038/nn828. PMID   11896398. S2CID   24021203.
  8. ↑ Nerlov, C.; Graf, T. (1998). "PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors". Genes & Development. 12 (15): 2403–2412. doi:10.1101/gad.12.15.2403. PMC   317050 . PMID   9694804.
  9. ↑ Xie, H.; Ye, M.; Feng, R.; Graf, T. (2004). "Stepwise reprogramming of B cells into macrophages". Cell. 117 (5): 663–676. doi: 10.1016/s0092-8674(04)00419-2 . PMID   15163413.
  10. ↑ Si-Tayeb, K.; Noto, F. K.; Sepac, A.; Sedlic, F.; Bosnjak, Z. J.; Lough, J. W.; Duncan, S. A. (2010). "Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors". BMC Developmental Biology. 10: 81. doi: 10.1186/1471-213X-10-81 . PMC   2923111 . PMID   20682060.
  11. ↑ Feng, R.; Desbordes, S. C.; Xie, H.; Tillo, E. S.; Pixley, F.; Stanley, E. R.; Graf, T. (2008). "PU.1 and C/EBP / convert fibroblasts into macrophage-like cells". Proceedings of the National Academy of Sciences. 105 (16): 6057–6062. doi: 10.1073/pnas.0711961105 . PMC   2327209 . PMID   18424555.
  12. ↑ Ieda, M.; Fu, J. D.; Delgado-Olguin, P.; Vedantham, V.; Hayashi, Y.; Bruneau, B. G.; Srivastava, D. (2010). "Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors". Cell. 142 (3): 375–386. doi:10.1016/j.cell.2010.07.002. PMC   2919844 . PMID   20691899.
  13. ↑ Huang, P.; He, Z.; Ji, S.; Sun, H.; Xiang, D.; Liu, C.; Hu, Y.; Wang, X.; Hui, L. (2011). "Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors". Nature. 475 (7356): 386–389. doi:10.1038/nature10116. PMID   21562492. S2CID   1115749.
  14. ↑ Sekiya, S.; Suzuki, A. (2011). "Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors". Nature. 475 (7356): 390–393. doi:10.1038/nature10263. PMID   21716291. S2CID   205225695.
  15. ↑ Vierbuchen, T.; Ostermeier, A.; Pang, Z. P.; Kokubu, Y.; Südhof, T. C.; Wernig, M. (2010). "Direct conversion of fibroblasts to functional neurons by defined factors". Nature. 463 (7284): 1035–1041. doi:10.1038/nature08797. PMC   2829121 . PMID   20107439.
  16. ↑ Adler, A. F.; Grigsby, C. L.; Kulangara, K.; Wang, H.; Yasuda, R.; Leong, K. W. (2012). "Nonviral Direct Conversion of Primary Mouse Embryonic Fibroblasts to Neuronal Cells". Molecular Therapy: Nucleic Acids. 1 (7): e32–. doi:10.1038/mtna.2012.25. PMC   3411320 . PMID   23344148.
  17. ↑ Pang, Z. P.; Yang, N.; Vierbuchen, T.; Ostermeier, A.; Fuentes, D. R.; Yang, T. Q.; Citri, A.; Sebastiano, V.; Marro, S.; Südhof, T. C.; Wernig, M. (2011). "Induction of human neuronal cells by defined transcription factors". Nature. 476 (7359): 220–223. doi:10.1038/nature10202. PMC   3159048 . PMID   21617644.
  18. ↑ Yoo, A. S.; Sun, A. X.; Li, L.; Shcheglovitov, A.; Portmann, T.; Li, Y.; Lee-Messer, C.; Dolmetsch, R. E.; Tsien, R. W.; Crabtree, G. R. (2011). "MicroRNA-mediated conversion of human fibroblasts to neurons". Nature. 476 (7359): 228–231. doi:10.1038/nature10323. PMC   3348862 . PMID   21753754.
  19. ↑ Ambasudhan, R.; Talantova, M.; Coleman, R.; Yuan, X.; Zhu, S.; Lipton, S. A.; Ding, S. (2011). "Direct Reprogramming of Adult Human Fibroblasts to Functional Neurons under Defined Conditions". Cell Stem Cell. 9 (2): 113–118. doi:10.1016/j.stem.2011.07.002. PMC   4567246 . PMID   21802386.
  20. ↑ Pfisterer, U.; Kirkeby, A.; Torper, O.; Wood, J.; Nelander, J.; Dufour, A.; Bjorklund, A.; Lindvall, O.; Jakobsson, J.; Parmar, M. (2011). "Direct conversion of human fibroblasts to dopaminergic neurons". Proceedings of the National Academy of Sciences. 108 (25): 10343–10348. doi: 10.1073/pnas.1105135108 . PMC   3121829 . PMID   21646515.
  21. ↑ Caiazzo, M.; Dell'Anno, M. T.; Dvoretskova, E.; Lazarevic, D.; Taverna, S.; Leo, D.; Sotnikova, T. D.; Menegon, A.; Roncaglia, P.; Colciago, G.; Russo, G.; Carninci, P.; Pezzoli, G.; Gainetdinov, R. R.; Gustincich, S.; Dityatev, A.; Broccoli, V. (2011). "Direct generation of functional dopaminergic neurons from mouse and human fibroblasts". Nature. 476 (7359): 224–227. doi:10.1038/nature10284. PMID   21725324. S2CID   4344437.
  22. ↑ Addis, R. C.; Hsu, F. C.; Wright, R. L.; Dichter, M. A.; Coulter, D. A.; Gearhart, J. D. (2011). Muotri, Alysson Renato (ed.). "Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector". PLOS ONE. 6 (12): e28719. doi: 10.1371/journal.pone.0028719 . PMC   3235158 . PMID   22174877.
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