Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues.
Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues.
复制标题
DOI：
10.1038/s41587-021-01109-w
复制
发表时间：
2022-05
影响因子：
46.9
通讯作者：
Shibata, Darryl
中科院分区：
文献类型：
--
作者：
Gabbutt, Calum;Schenck, Ryan O.;Weisenberger, Daniel J.;Kimberley, Christopher;Berner, Alison;Househam, Jacob;Lakatos, Eszter;Robertson-Tessi, Mark;Martin, Isabel;Patel, Roshani;Clark, Susan K.;Latchford, Andrew;Barnes, Chris P.;Leedham, Simon J.;Anderson, Alexander R. A.;Graham, Trevor A.;Shibata, Darryl
记录细胞祖先的分子时钟突变得太慢，无法测量成年组织中细胞更新的短期动态。在这里，我们展示了波动的DNA甲基化标记可以用作细胞中的时钟，在细胞中，正在进行的甲基化和去甲基化导致甲基化和非甲基化状态之间的重复“触发器”。我们使用标准甲基化阵列识别内源性波动CpG(FCpG)位点，并开发一个数学模型来从这些数据中定量测量人类成年干细胞的动态。据推测，小肠隐窝包含的干细胞略多于结肠，而小肠中的干细胞替换速度较慢。生殖系APC突变增加了每个隐窝的替换数量。在血液中，我们测量了急性白血病的快速扩张和慢性病的缓慢增长。因此，人类体细胞的出生和死亡模式是可以用波动的甲基化时钟(FMCS)来测量的。人类干细胞的谱系追踪是通过测量波动的DNA甲基化来实现的。
Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated ‘flip–flops’ between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than the colon, with slower stem cell replacement in the small intestine. Germline APC mutation increased the number of replacements per crypt. In blood, we measured rapid expansion of acute leukemia and slower growth of chronic disease. Thus, the patterns of human somatic cell birth and death are measurable with fluctuating methylation clocks (FMCs). Lineage tracing of human stem cells is achieved by measuring fluctuating DNA methylation.
登录
查看更多内容
影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
7.3
作者：
CAMPBELL, F;FULLER, CE;WILLIAMS, ED
通讯作者：
WILLIAMS, ED
DOI：
10.1073/pnas.0505903103
发表时间：
2006-01-17
影响因子：
11.1
作者：
Greaves, LC;Preston, SL;McDonald, SAC
通讯作者：
McDonald, SAC
DOI：
10.1073/pnas.1220353110
发表时间：
2013-07-02
影响因子：
11.1
作者：
Humphries, Adam;Cereser, Biancastella;Graham, Trevor A.
通讯作者：
Graham, Trevor A.