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Hematopoietic stem cells convert into liver cells within days without fusion


Both plasticity and cell fusion have been suggested to have a role in germ-layer switching1,2,3,4,5,6,7. To understand the mechanisms underlying cell fate changes, we have examined a highly enriched population of hematopoietic stem cells (HSCs)8,9,10 in vitro or in vivo in response to injury for liver-specific phenotypic and functional changes. Here we show that HSCs become liver cells when cocultured with injured liver separated by a barrier. Chromosomal analyses and tissue-specific gene and/or protein expression show that microenvironmental cues rather than fusion are responsible for conversion in vitro. We transplanted HSCs into liver-injured mice and observed that HSCs convert into viable hepatocytes with increasing injury. Notably, liver function was restored 2–7 d after transplantation. We conclude that HSCs contribute to the regeneration of injured liver by converting into functional hepatocytes without fusion.

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Figure 1: Differentiation of HSCs.
Figure 2: Conversion of HSCs.
Figure 3: Analysis of gene expression after 48 h coculture.
Figure 4: Engraftment of male HSCs after transplant into liver-injured female recipients.


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We thank R. Brodsky, N. Watkins, F. Yan and J. Haymann for discussions and critically evaluating the manuscript; and Z. Ye and W. Schuler for technical assistance. We appreciate financial support from the Ludwig Foundation and The Institute for Cellular Engineering at Johns Hopkins, and grants from the NIH.

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Correspondence to Saul J. Sharkis.

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Jang, YY., Collector, M., Baylin, S. et al. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 6, 532–539 (2004).

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