供体年龄和C1orf132/MIR29B2C决定异基因造血干细胞移植后血液中与年龄相关的甲基化特征。
Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.
作者信息
Spólnicka Magdalena, Piekarska Renata Zbieć, Jaskuła Emilia, Basak Grzegorz W, Jacewicz Renata, Pięta Agnieszka, Makowska Żanetta, Jedrzejczyk Maciej, Wierzbowska Agnieszka, Pluta Agnieszka, Robak Tadeusz, Berent Jarosław, Branicki Wojciech, Jędrzejczak Wiesław, Lange Andrzej, Płoski Rafał
机构信息
Biology Department, Central Forensic Laboratory of the Police, Warsaw, 00-583 Poland.
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, 53-114 Poland ; Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, 53-439 Poland.
出版信息
Clin Epigenetics. 2016 Sep 6;8(1):93. doi: 10.1186/s13148-016-0257-7. eCollection 2016.
BACKGROUND
Our recent study demonstrated that DNA methylation status in a set of CpGs located in ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood.
METHODS
DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing. DNA was isolated from the whole blood collected from recipients 27-360 days (mean 126) after HSCT and from the donors shortly before the HSCT.
RESULTS
It was found that in the recipients, the predicted age did not correlate with their calendar age but was correlated with the calendar age (r = 0.94, p = 4 × 10(-8)) and predicted age (r = 0.97, p = 5 × 10(-10)) of a respective donor. Despite this strong correlation, the predicted age of a recipient was consistently lower than the predicted age of a donor by 3.7 years (p = 7.8 × 10(-4)). This shift was caused by hypermethylation of the C1orf132 CpGs, for C1orf132 CpG_1. Intriguingly, the recipient-donor methylation difference correlated with calendar age of the donor (r = 0.76, p = 6 × 10(-4)). This finding could not trivially be explained by shifts of the major cellular factions of blood.
CONCLUSIONS
We confirm the single previous report that after HSCT, the age of the donor is the major determinant of age-specific methylation signature in recipient's blood. A novel finding is the unique methylation dynamics of C1orf132 which encodes MIR29B2C implicated in the self-renewing of hematopoietic stem cells. This observation suggests that C1orf132 could influence graft function after HSCT.
背景
我们最近的研究表明，位于ELOVL2、C1orf132、TRIM59、KLF14和FHL2基因座上的一组CpG位点的DNA甲基化状态能够准确预测血液中的实际年龄。在本研究中，我们使用这些标志物来评估异基因造血干细胞移植（HSCT）对人血液中与年龄相关的甲基化特征的影响。
方法
采用焦磷酸测序法对16对供受者的32个CpG位点的DNA甲基化进行研究。DNA取自HSCT术后27 - 360天（平均126天）的受者全血以及HSCT术前不久的供者全血。
结果
研究发现，在受者中，预测年龄与实际年龄不相关，但与相应供者的实际年龄（r = 0.94，p = 4×10⁻⁸）和预测年龄（r = 0.97，p = 5×10⁻¹⁰）相关。尽管存在这种强相关性，但受者的预测年龄始终比供者的预测年龄低3.7岁（p = 7.8×10⁻⁴）。这种偏移是由C1orf132基因座中C1orf132 CpG_1的CpG位点的高甲基化引起的。有趣的是，受者与供者之间的甲基化差异与供者的实际年龄相关（r = 0.76，p = 6×10⁻⁴）。这一发现不能简单地用血液中主要细胞成分的变化来解释。
结论
我们证实了之前唯一的一份报告，即HSCT术后，供者年龄是受者血液中年龄特异性甲基化特征的主要决定因素。一个新的发现是C1orf132具有独特的甲基化动态变化，C1orf132编码与造血干细胞自我更新有关的MIR29B2C。这一观察结果表明，C1orf132可能会影响HSCT术后的移植物功能。
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