Robust cellular reprogramming occurs spontaneously during liver regeneration
- Kilangsungla Yanger1,2,6,
- Yiwei Zong1,2,6,
- Lara R. Maggs1,2,
- Suzanne N. Shapira1,2,
- Ravi Maddipati1,2,
- Nicole M. Aiello1,2,
- Swan N. Thung3,
- Rebecca G. Wells1,
- Linda E. Greenbaum4 and
- Ben Z. Stanger1,2,5,7
- 1Department of Medicine, Gastroenterology Division,
- 2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
- 3Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA;
- 4Department of Cancer Biology, Jefferson University School of Medicine, Philadelphia, Pennsylvania 19107, USA;
- 5Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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↵6 These authors contributed equally to this work.
Abstract
Cellular reprogramming—the ability to interconvert distinct cell types with defined factors—is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
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Footnotes
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↵7 Corresponding author.
E-mail bstanger{at}exchange.upenn.edu
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.207803.112.
- Received October 8, 2012.
- Accepted February 25, 2013.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press