A decade of questions about the fluidity of cell identity

Masserdotti, Giacomo; Götz, Magdalena

doi:10.1038/d41586-020-00479-6

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24 February 2020

A decade of questions about the fluidity of cell identity

A method for directly converting connective-tissue cells into neurons opened up a new branch of research into cell-based therapies and called into question long-held beliefs about how development affects a cell’s identity.

Giacomo Masserdotti⁰ &
Magdalena Götz¹

Giacomo Masserdotti
1. Giacomo Masserdotti is in the Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, Munich 82152, Germany, and at the Institute for Stem Cell Research, Helmholtz Center Munich.
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Magdalena Götz
1. Magdalena Götz is in the Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, Munich 82152, Germany, and at the Institute for Stem Cell Research, Helmholtz Center Munich, and in the Excellence Cluster of Systems Neurology (SYNERGY), Munich, and is an external member of the Max-Planck Institute of Biochemistry, Martinsried.
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Our bodies rely on specialized cell types: brain cells compute information, red blood cells bind oxygen, and so on. Because almost all our cells have identical DNA, different patterns of gene and protein expression are needed to define these cell types. The selection and maintenance of these expression cascades were once thought to be irreversible after development. Over time, it emerged that cell identity could be changed, but it was often assumed that a cell could be converted into another cell type only if the two had a similar developmental origin. Ten years ago, Vierbuchen et al.¹ overthrew this idea, by showing that connective-tissue cells called fibroblasts could be converted into functional neurons — which have a very different developmental origin — if they were engineered to express just three extra transcription factors.

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Nature 578, 522-524 (2020)

doi: https://doi.org/10.1038/d41586-020-00479-6

References

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[1] Vierbuchen, T. et al. Nature 463, 1035–1041 (2010).
Article PubMed Google Scholar

[2] Mangold, O. & Spemann, H. Wilhelm Roux Arch. Entwickl. Mech. Org. 111, 341–422 (1927).
Article PubMed Google Scholar

[3] Gurdon, J. B. J. Embryol. Exp. Morphol. 10, 622–640 (1962).
PubMed Google Scholar

[4] Davis, R. L., Weintraub, H. & Lassar, A. B. Cell 51, 987–1000 (1987).
Article PubMed Google Scholar

[5] Heins, N. et al. Nature Neurosci. 5, 308–315 (2002).
Article PubMed Google Scholar

[6] Buffo, A. et al. Proc. Natl Acad. Sci. USA 102, 18183–18188 (2005).
Article PubMed Google Scholar

[7] Barker, R. A., Götz, M. & Parmar, M. Nature 557, 329–334 (2018).
Article PubMed Google Scholar

[8] Xu, J., Du, Y. & Deng, H. Cell Stem Cell 16, 119–134 (2015).
Article PubMed Google Scholar

[9] Takahashi, K. & Yamanaka, S. Cell 126, 663–676 (2006).
Article PubMed Google Scholar

[10] Pang, Z. P. et al. Nature 476, 220–223 (2011).
Article PubMed Google Scholar

[11] Caiazzo, M. et al. Nature 476, 224–227 (2011).
Article PubMed Google Scholar

[12] Son, E. Y. et al. Cell Stem Cell 9, 205–218 (2011).
Article PubMed Google Scholar

[13] Victor, M. B. et al. Neuron 84, 311–323 (2014).
Article PubMed Google Scholar

[14] Mertens, J. et al. Cell Stem Cell 17, 705–718 (2015).
Article PubMed Google Scholar

[15] Hu, W. et al. Cell Stem Cell 17, 204–212 (2015).
Article PubMed Google Scholar

[16] Victor, M. B. et al. Nature Neurosci. 21, 341–352 (2018).
Article PubMed Google Scholar

[17] Wapinski, O. L. et al. Cell 155, 621–635 (2013).
Article PubMed Google Scholar

[18] Rouaux, C. & Arlotta, P. Nature Cell Biol. 15, 214–221 (2013).
Article PubMed Google Scholar

[19] Gascon, S., Masserdotti, G., Russo, G. L. & Götz, M. Cell Stem Cell 21, 18–34 (2017).
Article PubMed Google Scholar

[20] von Schimmelmann, M. et al. Nature Neurosci. 19, 1321–1330 (2016).
Article PubMed Google Scholar

A decade of questions about the fluidity of cell identity

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