Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

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Fol. Biol. 2019, 65, 109-123

https://doi.org/10.14712/fb2019065030109

Reprogramming of Human Pancreatic Organoid Cells into Insulin-Producing β-Like Cells by Small Molecules and in Vitro Transcribed Modified mRNA Encoding Neurogenin 3 Transcription Factor

Tomas Koblas1,2, Ivan Leontovyč1,2, S. Loukotova2, F. Saudek3

1Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
2First Faculty of Medicine, Charles University, Prague, Czech Republic
3Department of Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Received June 2019
Accepted June 2019

References

1. Afrikanova, I., Yebra, M., Simpkinson, M., Xu, Y., Hayek, A., Montgomery, A. (2011) Inhibitors of Src and focal adhesion kinase promote endocrine specification: impact on the derivation of β-cells from human pluripotent stem cells. J. Biol. Chem. 286, 36042-52. <https://doi.org/10.1074/jbc.M111.290825>
2. Aguayo-Mazzucato, C., Bonner-Weir, S. (2018) Pancreatic β-cell regeneration as a possible therapy for diabetes. Cell Metabolism 27, 57-67. <https://doi.org/10.1016/j.cmet.2017.08.007>
3. Bruin, J. E., Suheda, E., Vela, J., Hu, X., Johnson, J. D., Kurata, H. T., Lynn, F. C., Piret, J. M., Asadi, A., Rezania, A., Kieffer, T. J. (2014) Characterization of polyhormonal insulin- producing cells derived in vitro from human embryonic stem cells. Stem Cell Res. 12, 194-208. <https://doi.org/10.1016/j.scr.2013.10.003>
4. Cavazzana-Calvo, M., Payen, E., Negre, O., Wang, G., Hehir, K., Fusil, F., Down, J., Denaro, M., Brady, T., Westerman, K., Cavallesco, R., Gillet-Legrand, B., Caccavelli, L., Sgarra, R., Maouche-Chrétien, L., Bernaudin, F., Girot, R., Dorazio, R., Mulder, G. J., Polack, A., Bank, A., Soulier, J., Larghero, J., Kabbara, N., Dalle, B., Gourmel, B., Socie, G., Chrétien, S., Cartier, N., Aubourg, P., Fischer, A., Cornetta, K., Galacteros, F., Beuzard, Y., Gluckman, E., Bushman, F., Hacein-Bey-Abina, S., Leboulch, P. (2010) Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 467, 318-22. <https://doi.org/10.1038/nature09328>
5. Dioum, E.M., Osborne, J.K., Goetsch, S., Russell, J., Schneider, J.W., Cobb, M.H. (2011) A small molecule differentiation inducer increases insulin production by pancreatic β cells. Proc. Natl. Acad. Sci. USA 108, 20713-20718. <https://doi.org/10.1073/pnas.1118526109>
6. Dorrell, C., Tarlow, B., Wang, Y., Canaday, P. S., Haft, A., Schug, J., Streeter, P. R., Finegold, M. J., Shenje, L. T., Kaestner, K. H., Grompe, M. (2014) The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar. Stem Cell Res. 13, 275-283. <https://doi.org/10.1016/j.scr.2014.07.006>
7. El-Gohary, Y., Wiersch, J., Tulachan, S., Xiao, X., Guo, P., Rymer, C., Fischbach, S., Prasadan, K., Shiote, C., Gaffar, I., Song, Z., Galambos, C., Esni, F., Gittes, G. K. (2016) Intraislet pancreatic ducts can give rise to insulin-positive cells. Endocrinology 157, 166-175. <https://doi.org/10.1210/en.2015-1175>
8. Fontcuberta-PiSunyer, M., Cervantes, S., Miquel, E., Mora-Castilla, S., Laurent, L. C., Raya, A., Gomis, R., Gasa, R. (2018) Modulation of the endocrine transcriptional program by targeting histone modifiers of the H3K27me3 mark. Biochim. Biophys. Acta Gene Regul. Mech. 1861, 473-480. <https://doi.org/10.1016/j.bbagrm.2018.03.003>
9. Furuyama, K., Chera, S., Gurp, L. V., Oropeza, D., Ghila, L., Damond, N., Vethe, H., Paolo, J. A., Joosten, A. M., Berney, T., Bosco, D., Dorrell, C., Grompe, M., Reader, H., Roep, B. O., Thorel, F., Herrera, P. L. (2019) Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells. Nature 567, 43-48. <https://doi.org/10.1038/s41586-019-0942-8>
10. Goparaju, S. K., Kohda, K., Ibata, K., Soma, A., Nakatake Y. (2017) Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci. Rep. 13, e42367. <https://doi.org/10.1038/srep42367>
11. Gosmain, Y., Katz, L. S., Masson, M. H., Cheyssac, C., Poisson, C., Philippe, J. (2012) Pax6 is crucial for β-cell function, insulin biosynthesis, and glucose-induced insulin secretion. Mol. Endocrinol. 26, 696-709. <https://doi.org/10.1210/me.2011-1256>
12. Gradwohl, G., Dierich, A., LeMeur, M., Guillemot, F. (2000) Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc. Natl. Acad. Sci. USA 97, 1607-1611. <https://doi.org/10.1073/pnas.97.4.1607>
13. Hacein-Bey-Abina, S., Kalle, C. V., Schmidt, M., McCormack, N. P., Leboulch, W. P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., Sorense, R., Forster, A., Fraser, P., Cohen, J. I., Basile, G. S., Alexander, I., Wintergerst, U., Frebourg, T., Aurias, A., Stoppa-Lyonnet, D., Romana, S., Radford-Weiss, I., Gross, F., Valensi, F., Delabesse E., Macintyre, E., Sigaux, F., Soulier, J., Leiva, L. E., Wissler, M., Prinz, C., Rabbitts, T. H., Deist, F. L., Fischer, A., Cavazzana-Calvo, M. (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415-419. <https://doi.org/10.1126/science.1088547>
14. Heinrich, C., Spagnoli, F. M., Berninger, B. (2015) In vivo reprogramming for tissue repair. Nat. Cell Biol. 17, 204-211. <https://doi.org/10.1038/ncb3108>
15. Hrvatin, S., Donnell C. W. O., Deng, F., Millman, J. R., Walton, F., Diiorio, P., Rezania, A., Gifford, D. K., Melton, D. A. (2014) Differentiated human stem cells resemble fetal, not adult, β-cells. Proc. Natl. Acad. Sci. USA 111, 3038-3043. <https://doi.org/10.1073/pnas.1400709111>
16. Huch, M., Bonfanti, P., Boj, S. F., Sato, T., Loomans, C. J. M., Wetering, M. V. D., Sojoodi, M., Li, V. S. W., Schuijers, J., Gracanin, A., Ringnalda, F., Begthel, H., Hamer, K., Mulder, J., Es, J. H., Koning, E., Vries, R. G. J., Heimberg, H., Clevers, H. (2013) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/Rspondin axis. EMBO J. 32, 2708-2721. <https://doi.org/10.1038/emboj.2013.204>
17. Jennings, R. E., Berry, A. A., Kirkwood-Wilson, R., Roberts, N. A., Hearn, T., Salisbury, R. J., Blaylock, J., Hanley, K. P., Hanley, N. A. (2013) Development of the human pancreas from foregut to endocrine commitment. Diabetes 62, 3514-3522. <https://doi.org/10.2337/db12-1479>
18. Jin, L., Gao, D., Feng, T., Tremblay, J. R., Ghazalli, N., Luo, A., Rawson, J., Quijano, J. C., Chai, J., Wedeken, L., Hsu, J., LeBon, J., Walker, S., Shih, H., Mahdavi, A., Tirrell, A., Riggs, A. D., Ku, H. T. (2016) Cells with surface expression of CD133 high CD71 low are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas. Stem Cell Res. 16, 40-53. <https://doi.org/10.1016/j.scr.2015.11.015>
19. Kim, B., Choi, S. W., Shin, J., Kim, J., Kang, I., Lee, B., Lee, J. Y., Kook, M. G. (2018) Single-factor SOX2 mediates direct neural reprogramming of human mesenchymal stem cells via transfection of in vitro transcribed mRNA. Cell Transplant. 27, 1154-1167. <https://doi.org/10.1177/0963689718771885>
20. Koblas, T., Pektorova, L., Zacharovova, K., Berkova, Z., Girman, P., Dovolilova, E., Karasova, L., Saudek, F. (2008) Differentiation of CD133-positive pancreatic cells into insulin- producing islet-like cell clusters. Transplant. Proc. 40, 415-418. <https://doi.org/10.1016/j.transproceed.2008.02.017>
21. Koblas, T., Leontovyc, I., Loukotova, S., Kosinova, L., Saudek, F. (2016) Reprogramming of pancreatic exocrine cells AR42J into insulin-producing cells using mRNAs for Pdx1, Ngn3, and MafA transcription factors. Mol. Ther. Nucleic Acids 5, e2016.33. <https://doi.org/10.1038/mtna.2016.33>
22. Lee, J., Sugiyama, T., Liu, Y., Wang, J., Gu, X., Lei, J., Markmann, J. F., Miyazaki, S., Miyazaki, J., Szot, G. L., Bottino, R., Kim, S. K. (2013) Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells. Elife 19, e00940 <https://doi.org/10.7554/eLife.00940>
23. Leontovyc, I., Habart, D., Loukotova, S., Kosinova, L., Kriz, J., Saudek, F., Koblas, T. (2017) Synthetic mRNA is a more reliable tool for the delivery of DNA-targeting proteins into the cell nucleus than fusion with a protein transduction domain. PLoS One 12, e0182497. <https://doi.org/10.1371/journal.pone.0182497>
24. Li, W., Cavelti-Weder, C., Zhang, Y., Clement, K., Donovan, S., Gonzalez, G., Zhu, J., Stemann, M., Xu, K., Hashimoto, T., Yamada, T., Nakanishi, M., Zhang, Y., Zeng, S., Gifford, D., Meisnner, A., Weir, G., Zhou, Q. (2014) Longterm persistence and development of induced pancreatic β cells generated by lineage conversion of acinar cells. Nat. Biotechnol. 32, 1223-1230. <https://doi.org/10.1038/nbt.3082>
25. Loomans, C. J. M., Giuliani, N. W., Balak, J., Ringnalda, F., Gurp, L., Huch, M., Boj, S. F., Sato, T., Kester, L., Lopes, S. M. C. S., Roots, M. S., Bonner-Weir, S., Engelse, M. A., Rabelink, T. J., Heimberg, H., Vries, R. G. J., Oudenaarden, A., Carlotti, F., Clevers, H., Koning, E. J. P. (2018) Expansion of adult human pancreatic tissue yields organoids harboring progenitor cells with endocrine differentiation potential. Stem Cell Reports 10, 712-724. <https://doi.org/10.1016/j.stemcr.2018.02.005>
26. Maechler, P., Wollheim, C. B. (2001) Mitochondrial function in normal and diabetic β-cells. Nature, 414, 807-812. <https://doi.org/10.1038/414807a>
27. Nishimura, W., Takahashi, S., Yasuda, K. (2015) MafA is critical for maintenance of the mature β cell phenotype in mice. Diabetologia 58, 566-574. <https://doi.org/10.1007/s00125-014-3464-9>
28. Rezania, A., Bruin, J. E., Riedel, M. J., Mojibian, M., Asadi, A., Xu, J., Gauvin, R., Narayan, K., Karanu, F., O’Neil, J. J., Ao, Z., Warnock, G. L., Kieffer, T. J. (2012) Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes 61, 2016-2029. <https://doi.org/10.2337/db11-1711>
29. Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., Dwyer, S. O., Quiskamp, N., Mojibian, M., Albrecht, T., Yang, Y. H. C., Johnson, J. D., Kieffer, T. J. (2014) Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32, 1121-1134. <https://doi.org/10.1038/nbt.3033>
30. Sancho, R., Gruber, R., Gu, G., Behrens, A. (2014) Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells. Cell Stem Cell 15, 139-353. <https://doi.org/10.1016/j.stem.2014.06.019>
31. Shapiro, A. M. J., Pokrywczynska, M., Ricordi, C. (2017) Clinical pancreatic islet transplantation. Nat. Rev. Endocrinol. 13, 268-277. <https://doi.org/10.1038/nrendo.2016.178>
32. Simeonov, K. P., Uppal, H. (2014) Direct reprogramming of human fibroblasts to hepatocyte-like cells by synthetic modified mRNAs. PLoS One 9, e0100134. <https://doi.org/10.1371/journal.pone.0100134>
33. Swales N., Matens G. A., Bonné, S., Heremans, Y., Borup, R., Casteele, M. V., Ling, Z., Pipeles, D., Ravassad, P., Nielsen, F., Ferre, J., Heimberg, H. (2012) Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming. PLoS One 7, e37055. <https://doi.org/10.1371/journal.pone.0037055>
34. Vieira, A., Vergoni, B., Courtney, M., Gjernes, E., Hadzic, B., Avolio, F., Napolitano, T., Navarro, S., Mansouri, A., Collombat, P. (2018) Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity. PLoS One 13, e201536.
35. Wang, S., Yan, J., Anderson, D. A., Xu, Y., Kanal, M. C., Cao, Z., Wright, C. V. E., Gu, G. (2010) Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev. Biol. 339, 26-37. <https://doi.org/10.1016/j.ydbio.2009.12.009>
36. Wang, Y., Dorrell, C., Naugler, W. E., Heskett, M., Spellman, P., Li, B., Galivo, F., Haft A., Wakefield, L., Grompe, M. (2018) Long-term correction of diabetes in mice by in vivo reprogramming of pancreatic ducts. Mol. Ther. 26, 1327-1342. <https://doi.org/10.1016/j.ymthe.2018.02.014>
37. Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y., Li, H., Lau, F., Ebina, W. (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618-630. <https://doi.org/10.1016/j.stem.2010.08.012>
38. Xu, X., D’Hoker, J., Stangé, S., Bonne, S., Leu, N. D., Xiao, X., Casteele, M. V. D., Mellitzer, G., Ling, Z., Pipeleers, D., Bouwens, L., Scharfmann, R., Gradwohl, G., Heimberg, H. (2008) β cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132, 197-207. <https://doi.org/10.1016/j.cell.2007.12.015>
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