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Nuclear Mechanics and Stem Cell Differentiation

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Abstract

Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

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References

  1. Zhang, F., & Pasumarthi, K. B. (2008). Embryonic stem cell transplantation: promise and progress in the treatment of heart disease. BioDrugs, 22(6), 61–74.

    Article  Google Scholar 

  2. Zhang, J. (2011). A human iPSC model of Hutchinson Gilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell, 8(1), 31–45.

    Article  CAS  PubMed  Google Scholar 

  3. Paolo, B., Mara, R., et al. (2001). Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells, 19, 180–192.

    Article  Google Scholar 

  4. Engler, A. J., et al. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 77–89.

    Article  Google Scholar 

  5. Guilak, F., et al. (2009). Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell, 5(1), 17–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Dahl, K. N., Booth-Gauthier, E. A., & Ladoux, B. (2010). In the middle of it all: mutual mechanical regulation between the nucleus and the cytoskeleton. Journal of Biomechanics, 43(1), 2–8.

    Article  PubMed  Google Scholar 

  7. Shivashankar, G. V. (2011). Mechanosignaling to the cell nucleus and gene regulation. Annual Review of Biophysics, 40, 361–378.

    Article  CAS  PubMed  Google Scholar 

  8. Melcer, S., et al. (2012). Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation. Nature Communications, 3, 910.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Pajerowski, J. D., et al. (2007). Physical plasticity of the nucleus in stem cell differentiation. PNAS, 104(40), 15619–15624.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ribeiro, A. J., & Dahl, K. N. (2012). The nuclear as a central structure in defining the mechanical properties of stem cells. In 32ed Annual International Conference of the IEEE EMBS (pp. 831–834).

    Google Scholar 

  11. Pekovic, V., & Hutchison, C. J. (2008). Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. Journal of Anatomy, 213(1), 5–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Zwerger, M., Ho, C. Y., & Lammerding, J. (2011). Nuclear mechanics in disease. Annual Review of Biomedical Engineering, 13, 397–428.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Dahl, K. N., Ribeiro, A. J., & Lammerding, J. (2008). Nuclear shape, mechanics, and mechanotransduction. Circulation Research, 102(11), 1307–1318.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Martins, R. P., et al. (2012). Mechanical regulation of nuclear structure and function. Annual Review of Biomedical Engineering, 14, 431–455.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Zhong, Z., Wilson, K. L., & Dahl, K. N. (2010). Beyond Lamins: other structural components of the nucleoskeleton. Methods in Cell Biology, 98, 97–119.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Philip, J. T., & Dahl, K. N. (2008). Nuclear mechanotransduction: response of the lamina to extracellular stress with implications in aging. Journal of Biomechanics, 41(15), 3164–3170.

    Article  PubMed  Google Scholar 

  17. Vaziri, A., & Mofrad, M. R. (2007). Mechanics and deformation of the nucleus in micropipette aspiration experiment. Journal of Biomechanics, 40(9), 2053–2062.

    Article  PubMed  Google Scholar 

  18. Constantinescu, D., et al. (2006). Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells, 24(1), 177–185.

    Article  CAS  PubMed  Google Scholar 

  19. Coffinier, C., Fong, L. G., & Young, S. G. (2010). LINCing lamin B2 to neuronal migration growing evidence for cell-specific roles of B-type lamins. Nucleus, 1(5), 407–411.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Lee, J. S., et al. (2007). Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophysics Journal, 93(7), 2542–2552.

    Article  CAS  Google Scholar 

  21. Deguchi, S., et al. (2005). Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. Journal of Biomechanics, 38(9), 1751–1759.

    Article  PubMed  Google Scholar 

  22. Akter, R., et al. (2009). Effect of lamin A/C knockdown on osteoblast differentiation and function. Journal of Bone and Mineral Research, 24(2), 283–293.

    Article  CAS  PubMed  Google Scholar 

  23. Prokocimer, M., et al. (2009). Nuclear lamins: key regulators of nuclear structure and activities. Journal of Cell and Molecular Medicine, 13(6), 1059–1085.

    Article  CAS  Google Scholar 

  24. Verstraeten, V. L., & Lammerding, J. (2008). Experimental techniques for study of chromatin mechanics in intact nuclei and living cells. Chromosome Research, 16(3), 499–510.

    Article  CAS  PubMed  Google Scholar 

  25. Horn, H. F., et al. (2013). The LINC complex is essential for hearing. Journal of Clinical Investigation, 123(2), 740–750.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Ho, C. Y., & Lammerding, J. (2012). Lamins at a glance. Journal of Cell Science, 125(9), 2087–2093.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Friedl, P., Wolf, K., & Lammerding, J. (2011). Nuclear mechanics during cell migration. Current Opinion in Cell Biology, 23, 55–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Espada, J., et al. (2008). Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. Journal of Cell Biology, 181(1), 27–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Houben, F., et al. (2009). Disturbed nuclear orientation and cellular migration in A-type lamin deficient cells. Biochemical Biophysics Acta, 1793(2), 312–324.

    Article  CAS  Google Scholar 

  30. Dahl, K. N., et al. (2006). Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome. PNAS, 103(27), 10271–10276.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Hampoelz, B., & Lecuit, T. (2011). Nuclear mechanics in differentiation and development. Current Opinion in Cell Biology, 23(6), 668–675.

    Article  CAS  PubMed  Google Scholar 

  32. Wheeler, M. A., et al. (2007). Distinct functional domains in nesprin-1α and nesprin-2β bind directly to emerin and both interactions are disrupted in X-linked Emery–Dreifuss muscular dystrophy. Experimental Cell Research, 313(13), 2845–2857.

    Article  CAS  PubMed  Google Scholar 

  33. Alexandre, M., & Tom, M. (2010). LINC complexes in health and disease. Nucleus, 1(1), 40–52.

    Article  Google Scholar 

  34. Khatau, S. B., et al. (2012). The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration. Scientific Reports, 2, 488.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Shyam, B. K., Dong-Hwee, K., et al. (2010). The perinuclear avtin cap in health and disease. Nucleus, 1(4), 337–342.

    Article  Google Scholar 

  36. Poh, Y. C., et al. (2010). Embryonic stem cells do not stiffen on rigid substrates. Biophysics Journal, 99(2), L19–L21.

    Article  CAS  Google Scholar 

  37. Kuznetsova, T. G., et al. (2007). Atomic force microscopy probing of cell elasticity. Micron, 38(8), 824–833.

    Article  CAS  PubMed  Google Scholar 

  38. Takai, E., et al. (2005). Osteoblast elastic modulus measured by atomic force microscopy is substrate dependent. Annuals of Biomedical Engineering, 33(7), 963–971.

    Article  Google Scholar 

  39. Qiu, H., et al. (2005). Short communication: vascular smooth muscle cell stiffness as a mechanism for increased aortic stiffness with aging. Circulation Research, 107(5), 615–619.

    Article  Google Scholar 

  40. Cross, S. E., et al. (2008). AFM-based analysis of human metastatic cancer cells. Nanotechnology, 19, 384003.

    Article  PubMed  Google Scholar 

  41. Xu, W., et al. (2012). Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PloS One, 7(10), e46609.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Ribeiro, A. J., et al. (2012). Mechanical characterization of adult stem cells from bone marrow and perivascular niches. Journal of Biomechanics, 45(7), 1280–1287.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Shin, J. W., Spinler, K. R., Swift, J., et al. (2013). Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America, 110(47), 18892–18897.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Harada, T., Swift, J., Irianto, J., et al. (2014). Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. Journal of Cell Biology, 204(5), 669–682.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Christiaan, H. R., Merel, L. R., et al. (2011). Robust nuclear lamina-besed cell classification of aging and senescent cells. Aging, 3(12), 1192–1201.

    Google Scholar 

  46. Swaminathan, V., et al. (2011). Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Research, 71(15), 5075–5080.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Meshorer, E., & Gruenbaum, Y. (2008). Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging. Journal of Cell Biology, 181(1), 9–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Smith, E. R., et al. (2011). Increased expression of Syne1/nesprin-1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation. Development Dynamics, 240(10), 2245–2255.

    Article  CAS  Google Scholar 

  49. Swift, J., Ivanovska, I. L., Buxboim, A., et al. (2013). Nuclear lamin-A scales with tissue stiffess and enhances matrix-directed differentiation. Science, 341(6149), 1240104.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Buxboim, A., Swift, J., Irianto, J., et al. (2014). Matrix elasticity regulates lamin-A, C phosphorylation and turnover with feedback to actomyosin. Current Biology, 24(16), 1909–1917.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Platt, I. D., & El-Sohemy, A. (2009). Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid. Journal of Nutrition Biochemistry, 20(12), 956–964.

    Article  CAS  Google Scholar 

  52. Gaur, T., et al. (2005). Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. Journal of Biology Chemistry, 280(39), 33132–33140.

    Article  CAS  Google Scholar 

  53. Li, W., et al. (2011). Decreased bone formation and osteopenia in lamin a/c-deficient mice. PloS One, 6(4), e19313.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Pan, D., et al. (2005). The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-beta superfamily of cytokines. Journal of Biology Chemistry, 280(16), 15992–16001.

    Article  CAS  Google Scholar 

  55. Ylva, R., Tomas, M., et al. (2011). stem cell depletion in Hutchinson-Gilford progeria syndrome. Aging Cell, 10, 1011–1020.

    Article  Google Scholar 

  56. Katherine, L. W., Michael, S. Z., & Kenneth, K. L. (2001). Lamins and disease: insights into nuclear infrastructure. Cell, 104, 647–650.

    Google Scholar 

  57. Rodriguez-Serrano, F., et al. (2010). Promotion of human adipose-derived stem cell proliferation mediated by exogenous nucleosides. Cell Biology International, 34(9), 917–924.

    Article  CAS  PubMed  Google Scholar 

  58. Willis, N. D., Wilson, R. G., & Hutchison, C. J. (2008). Lamin A: a putative colonic epithelial stem cell biomarker which identifies colorectal tumors with a more aggressive phenotype. Biochemical Society Transactions, 36(6), 1350–1353.

    Article  CAS  PubMed  Google Scholar 

  59. Ivanovska, I., et al. (2010). Physical plasticity of the nucleus and its manipulation. Methods in Cell Biology, 98, 207–220.

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 11272365), the Research Fund for the Doctoral Program of Higher Education of China (No. 20130191110029) and the Fundamental Research Funds for the Central Universities (106112015CDJZR238807).

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The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Xinjian Mao & Guanbin Song

  2. Institute of Bioengineering and School of Engineering & Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK

    Nuria Gavara

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  1. Xinjian Mao
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  2. Nuria Gavara
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Correspondence to Guanbin Song.

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Mao, X., Gavara, N. & Song, G. Nuclear Mechanics and Stem Cell Differentiation. Stem Cell Rev and Rep 11, 804–812 (2015). https://doi.org/10.1007/s12015-015-9610-z

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