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Nat Commun. 2013;4:2823. doi: 10.1038/ncomms3823.

Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology.

Author information

1
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
2
Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
#
Contributed equally

Abstract

Although organ fibrosis causes significant morbidity and mortality in chronic diseases, the lack of detailed knowledge about specific cellular contributors mediating fibrogenesis hampers the design of effective antifibrotic therapies. Different cellular sources, including tissue-resident and bone marrow-derived fibroblasts, pericytes and epithelial cells, have been suggested to give rise to myofibroblasts, but their relative contributions remain controversial, with profound differences between organs and different diseases. Here we employ a novel Cre-transgenic mouse that marks 99% of hepatic stellate cells (HSCs), a liver-specific pericyte population, to demonstrate that HSCs give rise to 82-96% of myofibroblasts in models of toxic, cholestatic and fatty liver disease. Moreover, we exclude that HSCs function as facultative epithelial progenitor cells in the injured liver. On the basis these findings, HSCs should be considered the primary cellular target for antifibrotic therapies across all types of liver disease.

PMID:
24264436
PMCID:
PMC4059406
DOI:
10.1038/ncomms3823
[Indexed for MEDLINE]
Free PMC Article

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