Skip to main content
Journal cover image

Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.

Publication ,  Journal Article
Yang, L; Jung, Y; Omenetti, A; Witek, RP; Choi, S; Vandongen, HM; Huang, J; Alpini, GD; Diehl, AM
Published in: Stem Cells
August 2008

Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic hepatic stellate cells (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote liver regeneration by producing growth factors for oval cells, bipotent progenitors of hepatocytes and cholangiocytes. Genes that are expressed by primary hepatic stellate cell (HSC) isolates overlap those expressed by oval cells, and hepatocytic and ductular cells emerge when HSC are cultured under certain conditions. We evaluated the hypothesis that HSC are a type of oval cell and, thus, capable of generating hepatocytes to regenerate injured livers. Because Q-HSC express glial fibrillary acidic protein (GFAP), we crossed mice in which GFAP promoter elements regulated Cre-recombinase with ROSA-loxP-stop-loxP-green fluorescent protein (GFP) mice to generate GFAP-Cre/GFP double-transgenic mice. These mice were fed methionine choline-deficient, ethionine-supplemented diets to activate and expand HSC and oval cell populations. GFP(+) progeny of GFAP-expressing precursors were characterized by immunohistochemistry. Basal expression of mesenchymal markers was negligible in GFAP(+)Q-HSC. When activated by liver injury or culture, HSC downregulated expression of GFAP but remained GFP(+); they became highly proliferative and began to coexpress markers of mesenchyme and oval cells. These transitional cells disappeared as GFP-expressing hepatocytes emerged, began to express albumin, and eventually repopulated large areas of the hepatic parenchyma. Ductular cells also expressed GFAP and GFP, but their proliferative activity did not increase in this model. These findings suggest that HSC are a type of oval cell that transitions through a mesenchymal phase before differentiating into hepatocytes during liver regeneration. Disclosure of potential conflicts of interest is found at the end of this article.

Duke Scholars

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

August 2008

Volume

26

Issue

8

Start / End Page

2104 / 2113

Location

England

Related Subject Headings

  • Stem Cells
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Mesoderm
  • Liver Regeneration
  • Liver Cirrhosis
  • Immunology
  • Immunohistochemistry
  • Hepatocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, L., Jung, Y., Omenetti, A., Witek, R. P., Choi, S., Vandongen, H. M., … Diehl, A. M. (2008). Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers. Stem Cells, 26(8), 2104–2113. https://doi.org/10.1634/stemcells.2008-0115
Yang, Liu, Youngmi Jung, Alessia Omenetti, Rafal P. Witek, Steve Choi, Hendrika M. Vandongen, Jiawen Huang, Gianfranco D. Alpini, and Anna Mae Diehl. “Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.Stem Cells 26, no. 8 (August 2008): 2104–13. https://doi.org/10.1634/stemcells.2008-0115.
Yang L, Jung Y, Omenetti A, Witek RP, Choi S, Vandongen HM, et al. Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers. Stem Cells. 2008 Aug;26(8):2104–13.
Yang, Liu, et al. “Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.Stem Cells, vol. 26, no. 8, Aug. 2008, pp. 2104–13. Pubmed, doi:10.1634/stemcells.2008-0115.
Yang L, Jung Y, Omenetti A, Witek RP, Choi S, Vandongen HM, Huang J, Alpini GD, Diehl AM. Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers. Stem Cells. 2008 Aug;26(8):2104–2113.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

August 2008

Volume

26

Issue

8

Start / End Page

2104 / 2113

Location

England

Related Subject Headings

  • Stem Cells
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Mesoderm
  • Liver Regeneration
  • Liver Cirrhosis
  • Immunology
  • Immunohistochemistry
  • Hepatocytes