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HL-60髓系分化的调控。生长与分化调控解偶联、S期特异性及两步调控的证据。

Control of HL-60 myeloid differentiation. Evidence of uncoupled growth and differentiation control, S-phase specificity, and two-step regulation.

作者信息

Yen A

出版信息

Exp Cell Res. 1985 Jan;156(1):198-212. doi: 10.1016/0014-4827(85)90274-5.

DOI:10.1016/0014-4827(85)90274-5
PMID:3855294
Abstract

Myeloid differentiation of HL-60 human promyelocytic leukemia cells was studied during DMSO-induced differentiation. G 1/0-specific growth arrest could occur without the usual associated subsequent phenotypic differentiation into mature myeloid cells, suggesting that growth arrest and phenotypic differentiation are separately regulated. In the course of differentiating, the cells achieved a semi-stable intermediate state where they had a labile, pre-commitment memory of exposure to inducer, but were not yet committed to differentiation. This state was associated with a nuclear structural change previously found to be associated with the precommitment memory state. The process of differentiation could thus be resolved into two steps, early events up through development of pre-commitment memory and late events subsequents to pre-commitment memory. The kinetics of terminal cell differentiation indicated that the cellular regulatory event initiating a program of differentiation in response to inducer was S phase-specific. A comparison of the present results for DSMO to previous results for retinoic acid (RA)-induced HL-60 myeloid differentiation showed that the two inducers effect different cellular pathways for differentiation of HL-60 cells to mature myeloid cells, but with certain common features including the above S-phase specificity and pre-commitment memory.

摘要

在二甲基亚砜(DMSO)诱导分化过程中,对HL-60人早幼粒细胞白血病细胞的髓系分化进行了研究。G1/0特异性生长停滞可能发生,而无需通常伴随的随后向成熟髓系细胞的表型分化,这表明生长停滞和表型分化是分别调控的。在分化过程中,细胞达到了一种半稳定的中间状态,在这种状态下,它们对诱导剂的暴露有一种不稳定的、预承诺记忆,但尚未致力于分化。这种状态与先前发现与预承诺记忆状态相关的核结构变化有关。因此,分化过程可以分为两个步骤,早期事件直至预承诺记忆的发展,以及预承诺记忆之后的晚期事件。终末细胞分化的动力学表明,响应诱导剂启动分化程序的细胞调节事件是S期特异性的。将目前关于二甲基亚砜(DMSO)的结果与先前关于维甲酸(RA)诱导的HL-60髓系分化的结果进行比较,发现这两种诱导剂影响HL-60细胞向成熟髓系细胞分化的不同细胞途径,但具有某些共同特征,包括上述S期特异性和预承诺记忆。

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Control of HL-60 myeloid differentiation. Evidence of uncoupled growth and differentiation control, S-phase specificity, and two-step regulation.HL-60髓系分化的调控。生长与分化调控解偶联、S期特异性及两步调控的证据。
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J Clin Invest. 1995 Mar;95(3):973-9. doi: 10.1172/JCI117806.
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Br J Cancer. 1995 May;71(5):937-41. doi: 10.1038/bjc.1995.181.
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