Changing potency by spontaneous fusion

Abstract

Recent reports have suggested that mammalian stem cells residing in one tissue may have the capacity to produce differentiated cell types for other tissues and organs19. Here we define a mechanism by which progenitor cells of the central nervous system can give rise to non-neural derivatives. Cells taken from mouse brain were co-cultured with pluripotent embryonic stem cells. Following selection for a transgenic marker carried only by the brain cells, undifferentiated stem cells are recovered in which the brain cell genome has undergone epigenetic reprogramming. However, these cells also carry a transgenic marker and chromosomes derived from the embryonic stem cells. Therefore the altered phenotype does not arise by direct conversion of brain to embryonic stem cell but rather through spontaneous generation of hybrid cells. The tetraploid hybrids exhibit full pluripotent character, including multilineage contribution to chimaeras. We propose that transdetermination consequent to cell fusion10 could underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells9.

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Figure 1: Isolation and identification of descendants of ES and CNS cells.
Figure 2: Morphology and chromosomal constitution.
Figure 3: Pluripotency of hybrid cells.
Figure 4: Contribution of ZIN40/HT2 hybrid cells to chimaeras.

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Acknowledgements

H. Niwa and I. Chambers generated the HT2 ES cells and Marios Stavridis the 46C cells. We thank C. Graham for directing us to the original studies of Barski and Ephrussi and are grateful to C. Blackburn and A. Medvinksy for comments on the manuscript. This research was supported by the International Human Frontiers Science Program and by the Medical Research Council and Biotechnology and Biological Sciences Research Council of the UK.

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Correspondence to Austin G. Smith.

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There is no patent filing or licensing agreement relating to the work

reported in this manuscript. A. Smith is a consultant to Stem Cell Sciences Ltd, a

biotechnology company specializing in embryonic stem cells. A. Smith also holds equity in

Stem Cell Sciences through a blind trust.

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Ying, Q., Nichols, J., Evans, E. et al. Changing potency by spontaneous fusion. Nature 416, 545–548 (2002). https://doi.org/10.1038/nature729

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