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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions.
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Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions.

机译：计数人体细胞复制：甲基化反映子宫内膜干细胞分裂。

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摘要

Cell proliferation may be altered in many diseases, but it is uncertain exactly how to measure total numbers of divisions. Although it is impossible to count every division directly, potentially total numbers of stem cell divisions since birth may be inferred from numbers of somatic errors. The idea is that divisions are surreptitiously recorded by random errors that occur during replication. To test this "molecular clock" hypothesis, epigenetic errors encoded in certain methylation patterns were counted in glands from 30 uteri. Endometrial divisions can differ among women because of differences in estrogen exposures or numbers of menstrual cycles. Consistent with an association between mitotic age and methylation, there was an age-related increase in methylation with stable levels after menopause, and significantly less methylation was observed in lean or older multiparous women. Methylation patterns were diverse and more consistent with niche rather than immortal stem cell lineages. There was no evidence for decreased stem cell survival with aging. An ability to count lifetime numbers of stem cell divisions covertly recorded by random replication errors provides new opportunities to link cell proliferation with aging and cancer.
机译：在许多疾病中，细胞增殖可能会发生变化，但尚不确定如何测量分裂总数。尽管不可能直接对每个分裂进行计数，但是从出生起就可能从体细胞错误的数量中推断出干细胞分裂的总数。想法是，复制过程中发生的随机错误会秘密记录分区。为了检验这种“分子钟”假说，在来自30个子宫的腺体中，对以某些甲基化模式编码的表观遗传错误进行了计数。妇女的子宫内膜分裂可能因雌激素暴露或月经周期数的差异而不同。与有丝分裂年龄和甲基化之间的关联一致，绝经后甲基化增加与年龄相关，且稳定水平，并且瘦或老年多胎妇女的甲基化明显减少。甲基化模式是多样的，并且与利基而不是永生的干细胞谱系更加一致。没有证据表明随着衰老干细胞存活率降低。计数由随机复制错误秘密记录的干细胞分裂的终生数目的能力提供了将细胞增殖与衰老和癌症联系起来的新机会。

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