Robust cellular reprogramming occurs spontaneously during liver regeneration

Kilangsungla Yanger, Yiwei Zong, Lara R. Maggs, Suzanne N. Shapira, Ravi Maddipati, Nicole M. Aiello, Swan N. Thung, Rebecca G. Wells, Linda E. Greenbaum, Ben Z. Stanger

Research output: Contribution to journalArticle

248 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-724
Number of pages6
JournalGenes and Development
Volume27
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Keywords

  • Facultative stem cells
  • Liver
  • Regeneration
  • Reprogramming

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Yanger, K., Zong, Y., Maggs, L. R., Shapira, S. N., Maddipati, R., Aiello, N. M., Thung, S. N., Wells, R. G., Greenbaum, L. E., & Stanger, B. Z. (2013). Robust cellular reprogramming occurs spontaneously during liver regeneration. Genes and Development, 27(7), 719-724. https://doi.org/10.1101/gad.207803.112