Volume 26, Issue 4 (7-2022)                   IBJ 2022, 26(4): 291-300 | Back to browse issues page

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Hasani Fard A H, Valizadeh M, Mazaheri Z, Hosseini J. MiR-106b-5p Regulates the Reprogramming of Spermatogonial Stem Cells into iPSC (Induced Pluripotent Stem Cell)-Like Cells. IBJ 2022; 26 (4) :291-300
URL: http://ibj.pasteur.ac.ir/article-1-3594-en.html
Background: Recent years have brought notable progress in raising the efficiency of the reprogramming technique so that approaches have evolved from known transgenic factors to only a few miRNAs. Nevertheless, there is a poor understanding of both the key factors and biological networks underlying this reprogramming. The present study aimed to investigate the potential of miR-106b-5p in regulating spermatogonial stem cells (SSCs) to induced pluripotent stem cell (iPSC)-like cells.
Methods: We used SSCs because pluripotency is inducible in SSCs under defined culture conditions, and they have a few issues compared to other adult stem cells. As both signaling and post-transcriptional gene controls are critical for pluripotency regulation, we traced the expression of Oct-4, Sox-2, Klf-4, c-Myc, and Nanog (OSKMN). Besides, we considered miR-106b-5p targets using bioinformatic methods.
Results: Our results showed that transfected SSCs with miR-106b-5p increased the expression of the OSKMN factors, which was significantly more than negative control groups. Moreover, using the functional miRNA enrichment analysis, online tools, and databases, we predicted that miR-106b-5p targeted a signaling pathway gene named MAPK1/ERK2, related to regulating stem cell pluripotency.
Conclusion: Together, our data suggest that miR-106b-5p regulates the reprogramming of SSCs into iPSC-like cells. Furthermore, noteworthy progress in the in vitro development of SSCs indicates promise reservoirs and opportunities for future clinical trials.
Type of Study: Full Length | Subject: Molecular Genetics & Genomics

1. Campos F. Adult stem cells and induced pluripotent stem cells for stroke treatment. Frontiers in neurology 2019; 10: 908. [DOI:10.3389/fneur.2019.00908]
2. Haake K, Ackermann M, Lachmann N. Concise review: Towards the clinical translation of induced pluripotent stem cell‐derived blood cells-ready for take‐off. Stem cells translational medicine 2019; 8(4): 332-339. [DOI:10.1002/sctm.18-0134]
3. Chen K, Long Q, Xing G, Wang T, Wu Y, Li L, Qi J, Zhou Y, Ma B, Schöler HR. Heterochromatin loosening by the Oct4 linker region facilitates Klf4 binding and iPSC reprogramming. The EMBO journal 2020; 39(1): e99165. [DOI:10.15252/embj.201899165]
4. Huang CY, Liu CL, Ting CY, Chiu YT, Cheng YC, Nicholson MW, Hsieh PC. Human iPSC banking: barriers and opportunities. Journal of biomedical science 2019; 26(1): 87. [DOI:10.1186/s12929-019-0578-x]
5. Takahashi K. Cellular reprogramming. Cold spring harbor perspectives in biology 2014; 6(2): a018606 [DOI:10.1101/cshperspect.a018606]
6. Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 2006; 440(7088): 1199-1203. [DOI:10.1038/nature04697]
7. Aponte PM. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine. World journal of stem cells 2015; 7(4): 669. [DOI:10.4252/wjsc.v7.i4.669]
8. Lee Y, Lee M, Lee SW, Choi NY, Ham S, Lee HJ, Ko K, Ko K. Reprogramming of spermatogonial stem cells into pluripotent stem cells in the spheroidal state. Animal cells and systems 2019; 23(6): 392-398. [DOI:10.1080/19768354.2019.1672578]
9. Jeong HS, Bhin J, Kim HJ, Hwang D, Lee DR, Kim KS. Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells. Experimental and molecular medicine 2017; 49(4): e315-e315. [DOI:10.1038/emm.2017.2]
10. Lüningschrör P, Hauser S, Kaltschmidt B, Kaltschmidt C. MicroRNAs in pluripotency, reprogramming and cell fate induction. Biochimica et biophysica acta (BBA)-molecular cell research 2013; 1833(8): 1894-1903. [DOI:10.1016/j.bbamcr.2013.03.025]
11. Farzaneh M, Alishahi M, Derakhshan Z, Sarani NH, Attari F, Khoshnam SE. The expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. Current stem cell research and therapy 2019; 14(3): 278-289. [DOI:10.2174/1574888X14666190123162402]
12. Pourrajab F, Zarch MB, BaghiYazdi M, Hekmatimoghaddam S, Zare-Khormizi MR. MicroRNA-based system in stem cell reprogramming; differentiation/dedifferentiation. The international journal of biochemistry and cell biology 2014; 55: 318-328. [DOI:10.1016/j.biocel.2014.08.008]
13. Ferreira AF, Calin GA, Picanço-Castro V, Kashima S, Covas DT, de Castro FA. Hematopoietic stem cells from induced pluripotent stem cells-considering the role of microRNA as a cell differentiation regulator. Journal of cell science 2018; 131(4): jcs203018. [DOI:10.1242/jcs.203018]
14. Xie D, Tong M, Xia B, Feng G, Wang L, Li A, Luo G, Wan H, Zhang Z, Zhang H, Yang YG, Zhou Q, Wang M, Wang XJ. Long noncoding RNA lnc-NAP sponges mmu-miR-139-5p to modulate Nanog functions in mouse ESCs and embryos. RNA biology 2021; 18(6): 875-887. [DOI:10.1080/15476286.2020.1827591]
15. Mei Y, Bian C, Li J, Du Z, Zhou H, Yang Z, Zhao RC. miR‐21 modulates the ERK-MAPK signaling pathway by regulating SPRY2 expression during human mesenchymal stem cell differentiation. Journal of cellular biochemistry 2013; 114(6): 1374-1384. [DOI:10.1002/jcb.24479]
16. Leonardo TR, Schultheisz HL, Loring JF, Laurent LC. The functions of microRNAs in pluripotency and reprogramming. Nature cell biology 2012; 14(11): 1114-1121. [DOI:10.1038/ncb2613]
17. Li Z, Yang CS, Nakashima K, Rana TM. Small RNA‐mediated regulation of iPS cell generation. The EMBO journal 2011; 30(5): 823-834. [DOI:10.1038/emboj.2011.2]
18. Hasani Fard AH, Mohseni Kouchesfehani H, Jalali H. Investigation of cholestasis‐related changes in characteristics of spermatogonial stem cells in testis tissue of male Wistar rats. Andrologia 2020: e13660. [DOI:10.1111/and.13660]
19. Ahmadi A, Moghadasali R, Ezzatizadeh V, Taghizadeh Z, Nassiri SM, Asghari-Vostikolaee MH, Alikhani M, Hadi F, Rahbarghazi R, Yazdi RS. Transplantation of mouse induced pluripotent stem cell-derived podocytes in a mouse model of membranous nephropathy attenuates proteinuria. Scientific reports 2019; 9(1): 1-13. [DOI:10.1038/s41598-019-51770-0]
20. Velasco V, Shariati SA, Esfandyarpour R. Microtechnology-based methods for organoid models. Microsystems and nanoengineering 2020; 6(1): 1-13. [DOI:10.1038/s41378-020-00185-3]
21. Bördlein A, Scherthan H, Nelkenbrecher C, Molter T, Bösl MR, Dippold C, Birke K, Kinkley S, Staege H, Will H. SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis. Journal of cell science 2011; 124(18): 3137-3148. [DOI:10.1242/jcs.085936]
22. Lee YJ, Ramakrishna S, Chauhan H, Park WS, Hong SH, Kim KS. Dissecting microRNA-mediated regulation of stemness, reprogramming, and pluripotency. Cell regeneration 2016; 5(1): 1-10. [DOI:10.1186/s13619-016-0028-0]
23. Adlakha YK, Seth P. The expanding horizon of MicroRNAs in cellular reprogramming. Progress in Neurobiology 2017; 148: 21-39. [DOI:10.1016/j.pneurobio.2016.11.003]
24. Anokye-Danso F, Snitow M, Morrisey EE. How microRNAs facilitate reprogramming to pluripotency. Journal of cell science 2012; 125(18): 4179-4787. [DOI:10.1242/jcs.095968]
25. Peskova L, Cerna K, Oppelt J, Mraz M, Barta T. Oct4-mediated reprogramming induces embryonic-like microRNA expression signatures in human fibroblasts. Scientific reports 2019; 9(1): 1-13. [DOI:10.1038/s41598-019-52294-3]
26. Mahabadi JA, Sabzalipoor H, Nikzad H, Seyedhosseini E, Enderami SE, Gheibi Hayat SM, Sahebkar A. The role of microRNAs in embryonic stem cell and induced pluripotent stem cell differentiation in male germ cells. Journal of cellular physiology 2019; 234(8): 12278-12289. [DOI:10.1002/jcp.27990]
27. He Z, Jiang J, Kokkinaki M, Tang L, Dobrinski I, Dym M. Regulation of spermatogonial stem cells by
28. microRNAs. Biology of reproduction 2011; 85: 42. [DOI:10.1093/biolreprod/85.s1.42]
29. He Z, Jiang J, Kokkinaki M, Tang L, Zeng W, Gallicano I, Dobrinski I, Dym M. MiRNA‐20 and mirna‐106a regulate spermatogonial stem cell renewal at the post‐transcriptional level via targeting STAT3 and Ccnd1. Stem cells 2013; 31(10): 2205-2217. [DOI:10.1002/stem.1474]
30. Kim MO, Kim SH, Cho YY, Nadas J, Jeong CH, Yao K, Kim DJ, Yu DH, Keum YS, Lee KY. ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4. Nature structural and molecular biology 2012; 19(3): 283. [DOI:10.1038/nsmb.2217]
31. Tsanov KM, Pearson DS, Wu Z, Han A, Triboulet R, Seligson MT, Powers JT, Osborne JK, Kane S, Gygi SP. LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency. Nature cell biology 2017; 19(1): 60-67. [DOI:10.1038/ncb3453]
32. Brumbaugh J, Russell JD, Yu P, Westphall MS, Coon JJ, Thomson JA. NANOG is multiply phosphorylated and directly modified by ERK2 and CDK1 in vitro. Stem cell reports 2014; 2(1): 18-25. [DOI:10.1016/j.stemcr.2013.12.005]
33. Brumbaugh J, Hou Z, Russell JD, Howden SE, Yu P, Ledvina AR, Coon JJ, Thomson JA. Phosphorylation regulates human OCT4. Proceedings of the national academy of sciences 2012; 109(19): 7162-7168. [DOI:10.1073/pnas.1203874109]
34. Saba-El-Leil MK, Frémin C, Meloche S. Redundancy in the world of MAP kinases: all for one. Frontiers in cell and developmental biology 2016; 4: 67. [DOI:10.3389/fcell.2016.00067]
35. Dhaliwal NK, Miri K, Davidson S, El Jarkass HT, Mitchell JA. KLF4 nuclear export requires ERK activation and initiates exit from naive pluripotency. Stem cell reports 2018; 10(4): 1308-1323. [DOI:10.1016/j.stemcr.2018.02.007]
36. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nature medicine 2013; 19(8): 998-1004. [DOI:10.1038/nm.3267]
37. Munro MJ, Wickremesekera SK, Peng L, Marsh RW, Itinteang T, Tan ST. Cancer stem cell subpopulations in primary colon adenocarcinoma. PloS one 2019; 14(9): e0221963. [DOI:10.1371/journal.pone.0221963]
38. Ballabio C, Anderle M, Gianesello M, Lago C, Miele E, Cardano M, Aiello G, Piazza S, Caron D, Gianno F. Modeling medulloblastoma in vivo and with human cerebellar organoids. Nature communications 2020; 11(1): 1-18. [DOI:10.1038/s41467-019-13989-3]
39. Villodre ES, Felipe KB, Oyama MZ, de Oliveira FH, da Costa Lopez PL, Solari C, Sevlever G, Guberman A, Lenz G. Silencing of the transcription factors Oct4, Sox2, Klf4, c-Myc or Nanog has different effect on teratoma growth. Biochemical and biophysical research communications 2019; 517(2): 324-329. [DOI:10.1016/j.bbrc.2019.07.064]
40. Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell 2008; 133(2): 217-222. [DOI:10.1016/j.cell.2008.04.001]
41. Hasani Fard AH, Kamalipour F, Mazaheri Z, Hosseini SJ. Evaluation of MiR-106b-5p expression in the production of IPS-like cells from mice SSCs during the formation of teratoma and the three embryonic layers. Cell journal (yakhteh) 2022; 24(6): in press.

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