Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors.
OBJECTIVE
Evidence that bone marrow cells have trans-differentiating potential to hepatocytes has been described in recent reports. However, the molecular mechanism underlying this phenomenon is unclear. To address this issue, we investigated the parameters involved in the trans-differentiation of bone marrow cells into a hepatic lineage.


METHODS
Mouse BM cells were cultured in a collagen gel without or with growth factors including basic fibroblast growth factor. The expression of hepatocyte-specific markers, cholangiocyte-specific marker and liver-enriched transcription factors was identified by RT-PCR and immunohistochemistry.


RESULTS
Basic fibroblast growth factor was found to be the most effective for inducing albumin in cultured BM cells. Furthermore, on stimulation of basic fibroblast growth factor, BM cells were found to express other hepatocyte-specific markers and a cholangiocyte-specific marker. This conversion was found to be associated with the induction of transcription factors including hepatocyte nuclear factors and GATA family proteins.


CONCLUSIONS
We established an in vitro culture system in which mouse bone marrow cells could trans-differentiate to hepatic lineage cells in response to growth factors, without cell fusion. In particular, basic fibroblast growth factor has the ability to induce the trans-differentiation into hepatic lineage cells from BM cells.
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 B5 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yukiko
Y
Saji
Shinji
S
Tamura
Yuichi
Y
Yoshida
Shinichi
S
Kiso
Ayuko Saeki
AS
Iizuka
Hitoshi
H
Matsumoto
Takako
T
Kawasaki
Yoshihiro
Y
Kamada
Yuji
Y
Matsuzawa
Yasuhisa
Y
Shinomura
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D006133:Growth Substances / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000378:metabolism*
D000418:Albumins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C484171:Gata4 protein, mouse; C494760:Gata6 protein, mouse; D006133:Growth Substances; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2