Simultaneous regulation of miR-451 and miR-191 led to erythroid fate decision of mouse embryonic stem cell

Document Type: Original Article

Authors

1 Stem Cell Technology Research Center, Tehran, Iran

2 Department of Hematology, School of Medicine, Tarbiat Modares University, Tehran, Iran

3 Department of Immunology, School of Medicine, Tarbiat Modares University, Tehran, Iran

4 Blood Transfusion Research Center, High Institute for Education and Research in Transfusion Medicine, Tehran, Iran

5 Department of Hematology, School of Para Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

Abstract

Objective(s): Various microRNAs (miRNAs) are expressed during development of mammalian cells, when they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. miR-191 and miR-451 have been shown to be critical regulators of hematopoiesis and have important roles in the induction of erythroid fate decision. So, the aim of this study is investigation of the miR-191 and miR-451 roles in the controlling mouse embryonic stem cell (mESC) differentiation toward the erythroid lineage.
Materials and Methods: mESCs were infected with either pCDH-miR-Off-191 viruses in pCDH-miR-Off-191 group or simultaneously with pCDH-miR-Off-191 and pCDH-miR-451 lentiviruses in simultaneous  group. Then, the expression profiles of erythroid specific transcription factors and globin genes were analyzed using QRT-PCR on day 14 and 21 of differentiation. Flow cytometry analysis was used to evaluate of TER119 and CD235a erythroid specific surface markers.
Results: Gata-1, Klf-1, Epor and globin chains were found to be expressed in pCDH-miR-Off-191 and in simultaneous groups. The majority of globin chains showed changes in their expression levels with progression of differentiation from day 14 to day 21. Flow cytometry results showed that miR-451 up- regulation and miR-191 down-regulation is associated with the expression of TER119 and CD235a. Of these two groups analyzed, simultaneous group was most significantly potent in stimulation of erythroid fate decision of mESCs.
Conclusion: Together, present data demonstrate that down-regulation of miR-191 alone can enhance the differentiation of mESCs. However, the simultaneous effect of miR-451up-regulation and miR-191 down-regulation is much stronger and can have more practical use in artificial blood production.

Keywords

Main Subjects


1. Sarkar S. Artificial blood. Indian J Crit Care Med peer-reviewed, official publication of Indian Society of Critical Care Medicine 2008; 12:140-143.
2. Moradi S, Jahanian-Najafabadi A, Roudkenar MH. Artificial blood substitutes: first steps on the long route to clinical utility. Clin Med Insights Blood Disord 2016; 9:33-41.
3. Klein HG, Spahn DR, Carson JL. Red blood cell transfusion in clinical practice. Lancet 2007; 370:415-426.
4. Cabrales P, Intaglietta M. Blood substitutes: evolution from non-carrying to oxygen and gas carrying fluids. ASAIO 2013; 59:337-354.
5. Lowe K. Perfluorinated blood substitutes and artificial oxygen carriers. Blood Rev 1999; 13:171-184.
6. Giarratana M-C, Kobari L, Lapillonne H, Chalmers D, Kiger L, Cynober T, et al. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol 2005; 23:69-74.
7. Lapillonne H, Kobari L, Mazurier C, Tropel P, Giarratana M-C, Zanella-Cleon I, et al. Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine. Haematologica 2010; 95:1651-1659.
8. Kim HO. In-vitro stem cell derived red blood cells for transfusion: are we there yet? Yonsei Med J 2014; 55:304-309.
9. Xi J, Li Y, Wang R, Wang Y, Nan X, He L, et al. In vitro large scale production of human mature red blood cells from hematopoietic stem cells by coculturing with human fetal liver stromal cells. Biomed Res Int 2013; 1-12.
10. Wang Q, Huang Z, Xue H, Jin C, Ju X-L, Han J-DJ, et al. MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4. Blood 2008; 111:588-595.
11. Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci U S A 2005; 102:18081-18086.
12. Bianchi N, Zuccato C, Finotti A, Lampronti I, Borgatti M, Gambari R. Involvement of miRNA in erythroid differentiation. Epigenomics 2012; 4:51-65.
13. Yang GH, Wang F, Yu J, Wang XS, Yuan JY, Zhang JW. MicroRNAs are involved in erythroid differentiation control. J Cell Biochem 2009; 107:548-556.
14. Jin HL, Kim JS, Kim YJ, Kim SJ, Broxmeyer HE, Kim K-S. Dynamic expression of specific miRNAs during erythroid differentiation of human embryonic stem cells. Mol Cells 2012; 34:177-183.
15. Zhan M, Miller CP, Papayannopoulou T, Stamatoyannopoulos G, Song C-Z. MicroRNA expression dynamics during murine and human erythroid differentiation. Exp Hematol 2007; 35:1015-1025.
16. Kouhkan F, Hafizi M, Mobarra N, Mossahebi-Mohammadi M, Mohammadi S, Behmanesh M, et al. miRNAs: a new method for erythroid differentiation of hematopoietic stem cells without the presence of growth factors. Appl Biochem Biotechnol 2014; 172:2055-2069.
17. Lawrie CH. microRNA expression in erythropoiesis and erythroid disorders. Br J Haematol 2010; 150:144-151.
18. Listowski MA, Heger E, Bogusławska DM, Machnicka B, Kuliczkowski K, Leluk J, et al. microRNAs: fine tuning of erythropoiesis. Cell Mol Biol Lett 2012; 18:34.
19. Zhang L, Flygare J, Wong P, Lim B, Lodish HF. miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1. Genes Dev 2011; 25:119-124.
20. Gileles-Hillel A, Kheirandish-Gozal L, Gozal D. Hemoglobinopathies and sleep–The road less traveled. Sleep Med Rev 2015; 24:57-70.
21. Makala LH TC, Clay EL, Neunert C and Betty S.Pace. Fetal hemoglobin induction to treat b-hemoglobinopathies: From bench to bedside. J Hematol Transfus 2014;2:1018-1030.
22. Kouhkan F, Soleimani M, Daliri M, Behmanesh M, Mobarra N. miR-451 up-regulation, induce erythroid differentiation of CD133+ cells independent of cytokine cocktails. Iran J Basic Med Sci 2013; 16:756-763.
23. Obeidi N, Pourfathollah AA, Soleimani M, Zarif MN, Kouhkan F. The effect of mir-451 upregulation on erythroid lineage differentiation of murine embryonic stem cells. Cell J 2016; 18:165-178.
24. Fu Y-F, Du T-T, Dong M, Zhu K-Y, Jing C-B, Zhang Y, et al. Mir-144 selectively regulates embryonic α-hemoglobin synthesis during primitive erythropoiesis. Blood 2009; 113:1340-1349.
25. Rasmussen KD, Simmini S, Abreu-Goodger C, Bartonicek N, Di Giacomo M, Bilbao-Cortes D, et al. The miR-144/451 locus is required for erythroid homeostasis. J Exp Med 2010;207:1351-1358.
26. Guglielmelli P, Tozzi L, Bogani C, Iacobucci I, Ponziani V, Martinelli G, et al. Overexpression of microRNA-16-2 contributes to the abnormal erythropoiesis in polycythemia vera. Blood 2011; 117:6923-6927.
27. Lodish H, Flygare J, Chou S. From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones. IUBMB Life 2010; 62:492-496.
28. Richmond TD, Chohan M, Barber DL. Turning cells red: signal transduction mediated by erythropoietin. Trends Cell Biol 2005; 15:146-155.
29. Dore LC, Amigo JD, dos Santos CO, Zhang Z, Gai X, Tobias JW, et al. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A 2008; 105:3333-3338.
30. Bungert J, Engel JD. The role of transcription factors in erythroid development. Ann Med 1996; 28:47-55.
31. Yu D, dos Santos CO, Zhao G, Jiang J, Amigo JD, Khandros E, et al. miR-451 protects against erythroid oxidant stress by repressing 14-3-3ζ. Genes Dev 2010; 24:1620-1633.
32. Patrick DM, Zhang CC, Tao Y, Yao H, Qi X, Schwartz RJ, et al. Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3ζ. Genes Dev 2010; 24:1614-1619.
33. Dzierzak E, Philipsen S. Erythropoiesis: development and differentiation. Cold Spring Harb Perspect Med 2013; 3:a011601.
34. Nagpal N, Kulshreshtha R. miR-191: an emerging player in disease biology. Front Genet 2014; 5:99.
35. Byon JC, Papayannopoulou T. MicroRNAs: Allies or foes in erythropoiesis? J Cell Physiol 2012; 227:7-13.
36. Mohammdai-asl J, Ramezani A, Norozi F, Malehi AS, Asnafi AA, Far MAJ, et al. MicroRNAs in erythropoiesis and red blood cell disorders. Front Biol 2015; 10:321-332.
37. Kaneko H, Shimizu R, Yamamoto M. GATA factor switching during erythroid differentiation. Curr Opin Hematol 2010; 17:163-168.
38. Ohneda K, Yamamoto M. Roles of hematopoietic transcription factors GATA-1 and GATA-2 in the development of red blood cell lineage. Acta Haemato 2002; 108:237-245.
39. Amanatiadou EP, Papadopoulos GL, Strouboulis J, Vizirianakis IS. GATA1 and PU. 1 bind to ribosomal protein genes in erythroid cells: implications for ribosomopathies. PloS One 2015; 10:e0140077.