| Summary: | 碩士 === 慈濟大學 === 人類遺傳研究所 === 92 === Hepatocytes undergo phases of differentiation as they arise from the ventral foregut
endoderm, proliferate to form the liver buds, and mature by birth. Molecular
mechanisms underlying the specification of cells in the developing liver are still not
well understood. FGFs is expressed in a variety of sites during organogenesis,
particularly in sites where tissue interactions take place. We studies liver tissue by
RCAS-TVA system, including fetal hepatocytes proliferation、dfferentiation and liver
regeneration. Many important genes can be introducted into the liver by this system.
This system is based on the finding that RCAS retrovirus can specifically infect cells
with the TVA receptor. The TVA receptor is encoded from the avian tv-a gene and
which is regulated by albumin promoter in the transgenic mice. Therefore the receptor
is expressed specifically in the liver, We then introduce exogenous genes into the liver,
including RCAS-FGF8 and RCAS-FGF10. We have successfully introducted
RCAS-AP virus into fetal hepatocytes and liver, in vitro and in vivo as indicated by AP
staining. The in vitro culture of fetal hepatocytes can provide a good model for
studying cell proliferation and differentiation. We found that FGF10 and FGF8
promoted glycogen storage in the fetal hepatocytes, a FGF10 promoted fetal
hepatocytes maturation and differentiation, as indicated by the expression of many
maturation markers. The mechanism of molecular interactions between FGFs and other
signals will be addressed. In addition, FGF10 induced fetal hepatocytes proliferation in
vitro. For in vivo, FGF10 increased the ratio of liver to body weight after liver
regeneration for 5 days. On the contrary, knock-down FGF10 expression by siRNA
could delay liver regeneration and inhibit expression of the cell cycle-related genes. In
the future, we seek to understand other FGFs or signaling molecules involved in the
processes of liver development using the TVA system.
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