Massive expansion of multiple clones in the mouse hematopoietic system long after whole-body X-irradiation.
Massive expansion of multiple clones in the mouse hematopoietic system long after whole-body X-irradiation.
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DOI：
10.1038/s41598-022-21621-6
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发表时间：
2022-10-14
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
克隆造血（CH）在老年人中普遍存在，并与血液恶性肿瘤和心血管疾病有关。虽然原子弹幸存者患这些疾病的风险随着辐射剂量的增加而增加，但辐射暴露与CH之间的因果关系尚不清楚。本研究考察了3-Gy全身照射后12-18个月小鼠的辐射暴露是否会诱发CH。我们发现辐射相关的外周血髓细胞和红细胞分布宽度（RDW）增加。骨髓和非造血组织细胞的深度测序显示，12只辐照小鼠中有11只在造血系统中出现复发性体细胞突变，而6只未辐照小鼠中没有。受辐射小鼠的变异等位基因频率（VAFs）为> 0.02，平均每只小鼠5.8个；VAFs为>.1和/或缺失的突变普遍存在。在两只受辐射的小鼠中检查造血干细胞/祖细胞，发现在同一克隆和多个独立克隆中共存几种突变，这些克隆提供60-80%的骨髓核细胞。我们的研究结果表明，辐射暴露导致了大量CH的发展。此外，我们还描述了辐射诱导的CH突变。
Clonal hematopoiesis (CH) is prevalent in the elderly and associates with hematologic malignancy and cardiovascular disease. Although the risk of developing these diseases increases with radiation doses in atomic-bomb survivors, the causal relationship between radiation exposure and CH is unclear. This study investigated whether radiation exposure induces CH in mice 12–18 months after 3-Gy whole-body irradiation. We found radiation-associated increases in peripheral blood myeloid cells and red blood cell distribution width (RDW). Deep sequencing of bone marrow and non-hematopoietic tissue cells revealed recurrent somatic mutations specifically in the hematopoietic system in 11 of 12 irradiated mice but none in 6 non-irradiated mice. The irradiated mice possessed mutations with variant allele frequencies (VAFs) of > 0.02 on an average of 5.8 per mouse; mutations with VAFs of > 0.1 and/or deletion were prevalent. Examining hematopoietic stem/progenitor cells in two irradiated mice revealed several mutations co-existing in the same clones and multiple independent clones that deliver 60–80% of bone marrow nuclear cells. Our results indicate development of massive CH due to radiation exposure. Moreover, we have characterized mutations in radiation-induced CH.
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影响因子：
16.6
作者：
Adewoye, Adeolu B.;Lindsay, Sarah J.;Dubrova, Yuri E.;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.
影响因子：
56.9
作者：
Morton, Lindsay M.;Karyadi, Danielle M.;Stewart, Chip;Bogdanova, Tetiana, I;Dawson, Eric T.;Steinberg, Mia K.;Dai, Jieqiong;Hartley, Stephen W.;Schonfeld, Sara J.;Sampson, Joshua N.;Maruvka, Yosef E.;Kapoor, Vidushi;Ramsden, Dale A.;Carvajal-Garcia, Juan;Perou, Charles M.;Parker, Joel S.;Krznaric, Marko;Yeager, Meredith;Boland, Joseph F.;Hutchinson, Amy;Hicks, Belynda D.;Dagnall, Casey L.;Gastier-Foster, Julie M.;Bowen, Jay;Lee, Olivia;Machiela, Mitchell J.;Cahoon, Elizabeth K.;Brenner, Alina, V;Mabuchi, Kiyohiko;Drozdovitch, Vladimir;Masiuk, Sergii;Chepurny, Mykola;Zurnadzhy, Liudmyla Yu;Hatch, Maureen;de Gonzalez, Amy Berrington;Thomas, Gerry A.;Tronko, Mykola D.;Getz, Gad;Chanock, Stephen J.
通讯作者：
Chanock, Stephen J.
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
克隆造血突变与临床结局的关联：系统评价和荟萃分析。
影响因子：
12.8
作者：
Nowakowska, Malgorzata K.;Kim, Taebeom;Thompson, Mikayla T.;Bolton, Kelly L.;Deswal, Anita;Lin, Steven H.;Scheet, Paul;Wehner, Mackenzie R.;Nead, Kevin T.
通讯作者：
Nead, Kevin T.