Science China Life Sciences

, Volume 60, Issue 2, pp 168–177 | Cite as

Interplay of transcription factors and microRNAs during embryonic hematopoiesis

  • Xueping Gong
  • Ruihua Chao
  • Pengxiang Wang
  • Xiaoli Huang
  • Jingjing Zhang
  • Xiaozhou Zhu
  • Yanyang Zhang
  • Xue Yang
  • Chao Hou
  • Xiangjun Ji
  • Tieliu Shi
  • Yuan Wang
Open Access
Research Paper

Abstract

Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation have been described in the past, the epigenetic regulation of embryonic hematopoiesis remains to be fully described. Here, by utilizing an in vitro differentiation system of mouse embryonic stem cells (ESCs), we identified more than 20 microRNAs that were highly enriched in embryonic hematopoietic cells, including some (e.g. miR-10b, miR-15b, and miR-27a) with previously unknown functions in blood formation. Luciferase and gene expression assays further revealed combinational binding and regulation of these microRNAs by key transcription factors in blood cells. Finally, bioinformatics and functional analyses supported an interactive regulatory control between transcription factors and microRNAs in hematopoiesis.

Keywords

hematopoiesis embryonic stem cells microRNA 

Notes

Acknowledgements

The microarray work was performed at the sequence core facility of National Institute of Environmental Health Sciences (NIEHS). This study was supported by the Ministry of Science and Technology of China (2016YFA0100302, 2014CB964800), the National Natural Science Foundation of China (31471347, 30971522, 31271589), the Science and Technology Commission of Shanghai Municipality (11DZ2260300, 13JC1406402, 16JC1404200).

Supplementary material

11427_2016_168_MOESM1_ESM.xls (38 kb)
Table S1 Sequences of the Oligonulceotides

References

  1. Bartel, D.P. (2004). MicroRNAs. Cell 116, 281–297.CrossRefPubMedGoogle Scholar
  2. Bertrand, J.Y., Giroux, S., Cumano, A., and Godin, I. (2005). Hematopoietic stem cell development during mouse embryogenesis. Methods Mol Med 105, 273–288.PubMedGoogle Scholar
  3. Chao, R., Gong, X., Wang, L., Wang, P., and Wang, Y. (2015). CD71high population represents primitive erythroblasts derived from mouse embryonic stem cells. Stem Cell Res 14, 30–38.CrossRefPubMedGoogle Scholar
  4. Chen, C.Z., Li, L., Lodish, H.F., and Bartel, D.P. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83–86.CrossRefPubMedGoogle Scholar
  5. Chen, D., and Zhang, G. (2001). Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis. Exp Hematol 29, 971–980.CrossRefPubMedGoogle Scholar
  6. Cumano, A., Dieterlen-Lièvre, F., and Godin, I. (2000). The splanchnopleura/ AGM region is the prime site for the generation of multipotent hemopoietic precursors, in the mouse embryo. Vaccine 18, 1621–1623.CrossRefPubMedGoogle Scholar
  7. Dzierzak, E. (1999). Embryonic beginnings of definitive hematopoietic stem cells. Ann N Y Acad Sci 872, 256–264; discussion 262–254.CrossRefPubMedGoogle Scholar
  8. Elefanty, A.G., Robb, L., and Glenn Begley, C. (1997). Factors involved in leukaemogenesis and haemopoiesis. Baillieres Clin Haematol 10, 589–614.CrossRefPubMedGoogle Scholar
  9. Fatica, A., Rosa, A., Fazi, F., Ballarino, M., Morlando, M., De angelis, F.G., Caffarelli, E., Nervi, C., and Bozzoni, I. (2006). MicroRNAs and hematopoietic differentiation. Cold Spring Harb Symp Quant Biol 71, 205–210.CrossRefPubMedGoogle Scholar
  10. Fazi, F., Rosa, A., Fatica, A., Gelmetti, V., De Marchis, M.L., Nervi, C., and Bozzoni, I. (2005). A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPa regulates human granulopoiesis. Cell 123, 819–831.CrossRefPubMedGoogle Scholar
  11. Gangaraju, V.K., and Lin, H. (2009). MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol 10, 116–125.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Gao, X., Wu, T., Johnson, K.D., Lahvic, J.L., Ranheim, E.A., Zon, L.I., and Bresnick, E.H. (2016). GATA factor-G-protein-coupled receptor circuit suppresses hematopoiesis. Stem Cell Rep 6, 368–382.CrossRefGoogle Scholar
  13. Garzon, R., and Croce, C.M. (2008). MicroRNAs in normal and malignant hematopoiesis. Curr Opin Hematol 15, 352–358.CrossRefPubMedGoogle Scholar
  14. Godin, I., and Cumano, A. (2002). The hare and the tortoise: an embryonic haematopoietic race. Nat Rev Immunol 2, 593–604.PubMedGoogle Scholar
  15. Gruber, A.J., Grandy, W.A., Balwierz, P.J., Dimitrova, Y.A., Pachkov, M., Ciaudo, C., Nimwegen, E., and Zavolan, M. (2014). Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways. Nucleic Acids Res 42, 9313–9326.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hermiston, M.L., Xu, Z., and Weiss, A. (2003). CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 21, 107–137.CrossRefPubMedGoogle Scholar
  17. Houbaviy, H.B., Murray, M.F., and Sharp, P.A. (2003). Embryonic stem cell-specific microRNAs. Dev Cell 5, 351–358.CrossRefPubMedGoogle Scholar
  18. Judson, R.L., Babiarz, J.E., Venere, M., and Blelloch, R. (2009). Embryonic stem cell—specific microRNAs promote induced pluripotency. Nat Biotechnol 27, 459–461.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Keller, G., Kennedy, M., Papayannopoulou, T., and Wiles, M.V. (1993). Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 13, 473–486.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kennedy, M., D’Souza, S.L., Lynch-Kattman, M., Schwantz, S., and Keller, G. (2007). Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures. Blood 109, 2679–2687.PubMedPubMedCentralGoogle Scholar
  21. Kennedy, M., Firpo, M., Choi, K., Wall, C., Robertson, S., Kabrun, N., and Keller, G. (1997). A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493.CrossRefPubMedGoogle Scholar
  22. Kruse, E.A., Loughran, S.J., Baldwin, T.M., Josefsson, E.C., Ellis, S., Watson, D.K., Nurden, P., Metcalf, D., Hilton, D.J., Alexander, W.S., and Kile, B.T. (2009). Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci USA 106, 13814–13819.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kyba, M., and Daley, G. (2003). Hematopoiesis from embryonic stem cells: lessons from and for ontogeny. Exp Hematol 31, 994–1006.CrossRefPubMedGoogle Scholar
  24. Kyba, M., Perlingeiro, R.C.R., and Daley, G.Q. (2002). HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 109, 29–37.CrossRefPubMedGoogle Scholar
  25. Lensch, M.W., and Daley, G.Q. (2004). Origins of mammalian hematopoiesis: in vivo paradigms and in vitro models. Curr Top Dev Biol 60, 127–196.CrossRefPubMedGoogle Scholar
  26. Lohmann, F., and Bieker, J.J. (2008). Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment. Development 135, 2071–2082.CrossRefPubMedGoogle Scholar
  27. Long, Y., and Huang, H. (2015). On signaling pathways: hematopoietic stem cell specification from hemogenic endothelium. Sci China Life Sci 58, 1256–1261.CrossRefPubMedGoogle Scholar
  28. Mankertz, J., Hillenbrand, B., Tavalali, S., Huber, O., Fromm, M., and Schulzke, J.D. (2004). Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Biochem Biophys Res Commun 314, 1001–1007.CrossRefPubMedGoogle Scholar
  29. McKinney-Freeman, S.L., Lengerke, C., Jang, I.H., Schmitt, S., Wang, Y., Philitas, M., Shea, J., and Daley, G.Q. (2008). Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes. Blood 111, 4944–4953.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Medvinsky, A., and Dzierzak, E. (1996). Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897–906.CrossRefPubMedGoogle Scholar
  31. Mikkola, H.K.A. (2003). Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood 101, 508–516.CrossRefPubMedGoogle Scholar
  32. Morrison, S.J., Uchida, N., and Weissman, I.L. (1995). The biology of hematopoietic stem cells. Annu Rev Cell Dev Biol 11, 35–71.CrossRefPubMedGoogle Scholar
  33. Nerlov, C., and Graf, T. (1998). PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 12, 2403–2412.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Palis, J., Robertson, S., Kennedy, M., Wall, C., and Keller, G. (1999). Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073–5084.PubMedGoogle Scholar
  35. Patrick, D.M., Zhang, C.C., Tao, Y., Yao, H., Qi, X., Schwartz, R.J., Jun-Shen Huang, L., and Olson, E.N. (2010). Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3. Genes Dev 24, 1614–1619.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Porcher, C., Swat, W., Rockwell, K., Fujiwara, Y., Alt, F.W., and Orkin, S.H. (1996). The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86, 47–57.CrossRefPubMedGoogle Scholar
  37. Schmitt, R.M., Bruyns, E., and Snodgrass, H.R. (1991). Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes Dev 5, 728–740.CrossRefPubMedGoogle Scholar
  38. Starck, J., Weiss-Gayet, M., Gonnet, C., Guyot, B., Vicat, J.M., and Morle, F. (2010). Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation. Blood 116, 4795–4805.CrossRefPubMedGoogle Scholar
  39. Vasilatou, D., Papageorgiou, S., Pappa, V., Papageorgiou, E., and Dervenoulas, J. (2010). The role of microRNAs in normal and malignant hematopoiesis. Eur J Haematol 84, 1–16.CrossRefPubMedGoogle Scholar
  40. Wang, Q., Liu, X., Tang, N., Archambeault, D.R., Li, J., Song, H., Tang, C., He, B., Matzuk, M.M., and Wang, Y. (2013). GASZ promotes germ cell derivation from embryonic stem cells. Stem Cell Res 11, 845–860.CrossRefPubMedGoogle Scholar
  41. Wang, Y., Baskerville, S., Shenoy, A., Babiarz, J.E., Baehner, L., and Blelloch, R. (2008). Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation. Nat Genet 40, 1478–1483.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wang, Y., Yates, F., Naveiras, O., Ernst, P., and Daley, G.Q. (2005). Embryonic stem cell-derived hematopoietic stem cells. Proc Natl Acad Sci USA 102, 19081–19086.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Wilson, N.K., Foster, S.D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P.M., Kinston, S., Ouwehand, W.H., Dzierzak, E., Pimanda, J.E., de Bruijn, M.F.T.R., and Göttgens, B. (2010). Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 7, 532–544.CrossRefPubMedGoogle Scholar
  44. Xie, J.J., and Zhang, C.C. (2015). Ex vivo expansion of hematopoietic stem cells. Sci China Life Sci 58, 839–853.CrossRefPubMedGoogle Scholar
  45. Xie, X.Y., Li, Y.H., and Pei, X.T. (2014). From stem cells to red blood cells: how far away from the clinical application? Sci China Life Sci 57, 581–585.CrossRefPubMedGoogle Scholar
  46. Zhao, M., and Li, L.H. (2015). Regulation of hematopoietic stem cells in the niche. Sci China Life Sci 58, 1209–1215.PubMedGoogle Scholar

Copyright information

© The Author(s) 2016

Authors and Affiliations

  • Xueping Gong
    • 1
  • Ruihua Chao
    • 1
  • Pengxiang Wang
    • 1
  • Xiaoli Huang
    • 1
  • Jingjing Zhang
    • 1
  • Xiaozhou Zhu
    • 1
  • Yanyang Zhang
    • 1
  • Xue Yang
    • 1
  • Chao Hou
    • 1
  • Xiangjun Ji
    • 1
  • Tieliu Shi
    • 1
  • Yuan Wang
    • 1
  1. 1.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina

Personalised recommendations