DEPENDENCE OF LIVER-SPECIFIC TRANSCRIPTION ON TISSUE ORGANIZATION

DEPENDENCE OF LIVER-SPECIFIC TRANSCRIPTION ON TISSUE ORGANIZATION
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DOI:
10.1128/mcb.5.10.2623
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发表时间:
1985-01-01
影响因子:
5.3
通讯作者:
DARNELL, JE
DARNELL, JE
中科院分区:
生物学2区
文献类型:
--
作者:
CLAYTON, DF;HARRELSON, AL;DARNELL, JE

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当肝脏解体并将肝细胞作为细胞单层培养24小时时,大多数肝脏特异的mRNAs的转录急剧下降(下降80%至99%),但常见的mRNAs不发生(Clayton和Darnell,Mol.牢房。比奥尔。2:1552-1561,1983)。多种不同激素和底物的培养条件以及与其他细胞的共培养都未能维持培养的肝细胞中肝脏特异性mRNA的高合成,尽管它们继续以正常或高速率合成共同的mRNAs。相比之下,当将完整的小鼠肝组织切片置于培养中时,肝脏特异基因的转录保持在高水平(正常肝脏的20%至100%)。此外,我们还发现,通过在含血清的培养液中用EDTA灌流肝脏,肝脏中的细胞可以脱离并立即重新参与到组织样结构中。再接合的肝脏切片在培养24小时后继续以显著高于EDTA灌流分离的单个细胞转录组织特异性mRNA序列的速度进行单层培养。因此,我们得出结论,成熟的组织结构在维持肝细胞最大组织特异性转录方面起着重要作用。
When the liver is disaggregated and hepatocytes are cultured as a cellular monolayer for 24 h, a sharp decline (80 to 99% decrease) in the transcription of most liver-specific mRNAs, but not common mRNAs, occurs (Clayton and Darnell, Mol. Cell. Biol. 2:1552-1561, 1983). A wide variety of culture conditions involving various hormones and substrates and cocultivation with other cells failed to sustain high rates of liver-specific mRNA synthesis in cultured hepatocytes, although they continued to synthesize common mRNAs at normal or elevated rates. In contrast, when slices of intact mouse liver tissue were placed in culture, the transcription of liver-specific genes was maintained at high levels (20 to 100% of normal liver). Furthermore, we found that cells in the liver could be disengaged and immediately reengaged in a tissue-like structure by perfusing the liver with EDTA followed by serum-containing culture medium. Slices of reengaged liver continued to transcribe tissue-specific mRNA sequences at significantly higher rates after 24 h in culture than did individual cells isolated by EDTA perfusion followed by culturing as a monolayer. Therefore we conclude that a mature tissue structure plays an important role in the maintenance of maximum tissue-specific transcription in liver cells.