Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion

Nature Communications

Volumn 7, Issue , 2016, Pages

  Singh, Mandeep S ^a   Balmer, Jasmin ^a   Barnard, Alun R ^a   Aslam, Sher A ^a,b   Moralli, Daniela ^c   Green, Catherine M ^c   Barnea Cramer, Alona ^a   Duncan, Isabel ^a   MacLaren, Robert E ^a,b,d  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b MINISTRY OF DEFENCE   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d MOORFIELDS EYE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CARRIER PROTEIN; CRE RECOMBINASE; GREEN FLUORESCENT PROTEIN; PROTEIN PRECURSOR; INTEGRASE;

CELLS AND CELL COMPONENTS; CHROMOSOME; CYTOPLASM; DISEASE TREATMENT; EYE; RECOMBINATION; VISUAL CUE;

ADULT; ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL FUSION; CELL TRANSFER; CELL TRANSPLANTATION; CELLULAR DISTRIBUTION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; CYTOPLASM; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; HOST CELL; MALE; MOUSE; NONHUMAN; NUCLEAR ENERGY; PHOTORECEPTOR CELL; PROTEIN EXPRESSION; RETINA DEGENERATION; X CHROMOSOME; Y CHROMOSOME; ANIMAL; C57BL MOUSE; CYTOLOGY; DISEASE MODEL; GENETIC RECOMBINATION; GENETICS; HUMAN; PHYSIOLOGY; REGENERATION; RETINA; TRANSGENIC MOUSE; TRANSPLANTATION; VERTEBRATE PHOTORECEPTOR CELL;

ANIMALS; CELL FUSION; CYTOPLASM; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; INTEGRASES; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PHOTORECEPTOR CELLS, VERTEBRATE; RECOMBINATION, GENETIC; REGENERATION; RETINA; RETINAL DEGENERATION; X CHROMOSOME; Y CHROMOSOME;

EID: 84999289199     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms13537     Document Type: Article

References (22)

1. Bartsch, U. et al. Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice. Exp. Eye Res. 86, 691-700 (2008).
2. Kwan, A. S. L., Wang, S. & Lund, R. D. Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Exp. Neurol. 159, 21-33 (1999).
3. Lamba, D. A., Gust, J. & Reh, T. A. Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4, 73-79 (2009).
4. Lamba, D. A. et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS ONE 5, e8763 (2010).
5. MacLaren, R. E. et al. Retinal repair by transplantation of photoreceptor precursors. Nature 444, 203-207 (2006).
6. Singh, M. S. et al. Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation. Proc. Natl. Acad. Sci. USA 110, 1101-1106 (2013).
7. Pearson, R. A. et al. Restoration of vision after transplantation of photoreceptors. Nature 485, 99-103 (2012).
8. Gonzalez-Cordero, A. et al. Photoreceptor precursors derived from threedimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat. Biotechnol. 31, 741-747 (2013).
9. Vintersten, K. et al. Mouse in red: red fluorescent protein expression in mouse ES cells, embryos, and adult animals. Genesis 40, 241-246 (2004).
10. Akimoto, M. et al. Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proc. Natl Acad. Sci. USA 103, 3890-3895 (2006).
11. McDonald, J. H. & Dunn, K. W. Statistical tests for measures of colocalization in biological microscopy. J. Microsc. 252, 295-302 (2013).
12. Bowes, C. et al. Retinal degeneration in the rd mouse is caused by a defect in the b subunit of rod cGMP-phosphodiesterase. Nature 347, 677-680 (1990).
13. La Vail, M. M. & Sidman, R. L. C57BL-6J mice with inherited retinal degeneration. Arch. Ophthalmol. 91, 394-400 (1974).
14. Perez-Vargas, J. et al. Structural basis of eukaryotic cell-cell fusion. Cell 157, 407-419 (2014).
15. Podbilewicz, B. et al. The C. elegans developmental fusogen EFF-1 mediates homotypic fusion in heterologous cells and in vivo. Dev. Cell 11, 471-481 (2006).
16. Davis, D. M. & Sowinski, S. Membrane nanotubes: dynamic long-distance connections between animal cells. Nat. Rev. Mol. Cell Biol. 9, 431-436 (2008).
17. Valiunas, V. et al. Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. J. Physiol. 568, 459-468 (2005).
18. Alvarez-Dolado, M. & Martinez-Losa, M. Cell fusion and tissue regeneration. Adv. Exp. Med. Biol. 713, 161-175 (2011).
19. Lluis, F. & Cosma, M. P. Cell-fusion-mediated somatic-cell reprogramming: a mechanism for tissue regeneration. J. Cell. Physiol. 223, 6-13 (2010).
20. Lu, X. & Kang, Y. Cell fusion as a hidden force in tumor progression. Cancer Res. 69, 8536-8539 (2009).
21. Sanges, D. et al. Wnt/beta-catenin signaling triggers neuron reprogramming and regeneration in the mouse retina. Cell Rep. 4, 271-286 (2013).
22. Nishida, A. et al. Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat. Neurosci. 6, 1255-1263 (2003).