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Molecular medicine reports

Epigenetic modifications of histone H3 during the transdifferentiation of Thy-1(+) Lin(‑) bone marrow cells into hepatocytes.


PMID 26459745

Abstract

The epigenetic modifications during the transdifferentiation of adult stem cells remain to be fully elucidated. In the present study, the histone H3 modifications during the transdifferentiation of rat Thy‑1(+) Lin(‑) bone marrow cells into hepatocytes in vitro were examined, which involved performing hepatocyte growth factor-mediated transdifferentiation of bone marrow Thy-1(+) Lin(‑) cells into hepatic lineage cells. Subsequently, the hepatocyte-specific markers, cytokeratin‑18 (CK‑18), albumin (ALB) and α‑fetoprotein (AFP) were examined by immunofluorescence staining or reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Changes in the key pluripotency factor, octamer‑binding transcription factor 4 (OCT4) and histone modifications, including the dimethylation and acetylation of H3 at lysine 9 (H3K9me2 and H3K9ac), lysine 14 (H3K14me2 and H3K14ac) and lysine 27 (H3K27me2 and H3K27ac), were also investigated by RT-qPCR, immunofluorescence staining or western blot analysis The mRNA expression levels of AFP and ALB were detected in the bone marrow stem cell‑derived hepatic lineage cells on days 7 and 14 following induction, and CK‑18 was detected on day 14 following induction. During the transdifferentiation of the bone marrow Thy‑1(+) Lin(‑) cells into hepatocytes, the mRNA expression of OCT4 was significantly reduced, and the levels of H3K9me2, H3K9ac, H3K14me2, H3K14ac, H3K27me2 and H3K27ac were increased significantly, compared with the levels at baseline (P<0.05). Therefore, the results of the present study demonstrated that histone H3 modifications at lysine 9, 14 and 27 are involved in the regulation of transcription during the transdifferentiation of bone marrow stem cells to hepatic lineage cells.