Development

Following a New Program

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Science  12 Apr 2013:
Vol. 340, Issue 6129, pp. 123
DOI: 10.1126/science.340.6129.123-b
CREDIT: K. YANGER ET AL., GENES & DEVELOPMENT 27 (21 MARCH 2013) © 2013 COLD SPRING HARBOR LABORATORY PRESS

As illustrated in Greek mythology, in which an eagle feeds on Prometheus' liver each day, the amazing regenerative properties of the liver have long been known. An intriguing feature of liver regeneration is that it is context-specific: Excising part of the liver results in the growth or proliferation of existing cells, whereas exposure to toxic agents drives the accumulation of cells that have a biliary phenotype. Yanger et al. sought to determine whether cellular plasticity plays a role during liver response to injury and found that indeed it does. Toxin-induced injury of mouse hepatocytes generated cells that had the morphological, structural, and molecular features of normal biliary epithelial cells (BECs). Similar to BEC development, Notch signaling was required. Normal hepatocytes are binucleated; likewise, so were the BEC-like cells that were generated in response to injury, which suggests a hepatocyte origin. As cells went through the hepatocyte–to–BEC-like cell transition, they displayed an intermediate state where they co-expressed transcription factors of both cell types. The conversion of adult hepatocytes to BECs may find applicability in treatment of conditions with loss of these cells in humans.

Genes Dev. 27, 10.1101/gad.207803.112 (2013).

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