Spontaneous and radiation-induced differentiation of fibroblasts

Spontaneous and radiation-induced differentiation of fibroblasts
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DOI:
10.1016/s0531-5565(00)00168-6
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发表时间:
2000-09-01
影响因子:
3.9
通讯作者:
Rodemann, HP
Rodemann, HP
中科院分区:
医学2区
文献类型:
--
作者:
Herskind, C;Rodemann, HP

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来自所有年龄段供体的成纤维细胞培养物中的克隆异质性与成纤维细胞/纤维细胞系统的分化相关。因此,之前已经鉴定了终末分化谱系,其包括前体区室中的三种潜在有丝分裂祖细胞成纤维细胞(MFI -> MFII -> MFIII)和功能区室中的三种类型的有丝分裂后纤维细胞(PMFIV-> PMFV-> PMFVI)的序列。在本研究中,我们表明,从功能区室丢失的纤维细胞的补充预计不会改变在稳态人口的分化类型的分布,提供细胞损失发生在一个长序列的细胞分裂结束。然而,祖细胞成纤维细胞的过早终末分化为有丝分裂后的纤维细胞可以通过电离辐射和其他细胞应激源诱导。此外,即使是低剂量的1戈伊也会导致存活的MF祖细胞的分布发生变化,朝向前体隔室内的后期分化阶段。研究了成纤维细胞自分泌转化生长因子β 1在介导终末分化中的作用。我们建议,细胞应激和DNA损伤剂可能有助于随着年龄的分化状态的进展,个体差异可能与诱导分化率的差异有关。(C)2000 Elsevier Science Inc. All rights reserved.
Clonal heterogeneity in fibroblast cultures from donors of all ages has been associated with differentiation of the fibroblast/fibrocyte system. Thus, a terminal differentiation lineage including a sequence of three potentially mitotic progenitor fibroblasts (MFI --> MFII --> MFIII) in the precursor compartment and three types of postmitotic fibrocytes (PMFIV --> PMFV --> PMFVI) in the functional compartment has been identified previously. In the present study, we show that replenishment of fibrocytes lost from the functional compartment is not expected to change the distribution of differentiation types in a steady state population, provided cell loss occurs at the end of a long sequence of cell divisions only. However, premature terminal differentiation of progenitor fibroblasts to postmitotic fibrocytes can be induced by ionising radiation and other cell stressors, Furthermore, even a low dose of 1 Gy causes a change in the distribution of surviving MF progenitor cells towards later differentiation stages within the precursor compartment. The role of autocrine transforming growth factor-beta1 production by fibroblasts in mediating terminal differentiation was investigated. We propose that cell stress and DNA damaging agents may contribute to progression of the differentiation state with age and that individual variation may be related to differences in the rate of induced differentiation. (C) 2000 Elsevier Science Inc. All rights reserved.