Kyoizumi Seishi, Kubo Yoshiko, Misumi Munechika, Kajimura Junko, Yoshida Kengo, Hayashi Tomonori, Imai Kazue, Ohishi Waka, Nakachi Kei, Young Lauren F, Shieh Jae-Hung, Moore Malcolm A, van den Brink Marcel R M, Kusunoki Yoichiro
a Departments of Radiobiology/Molecular Epidemiology.
b Statistics and.
Radiat Res. 2016 Jan;185(1):69-76. doi: 10.1667/RR14209.1. Epub 2015 Dec 31.
It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.
目前尚不清楚造血干细胞和祖细胞（HSPCs）在近70年前遭受原子弹辐射的老年原子弹幸存者群体中是否受到损害。为了解决这个问题，我们评估了231名广岛原子弹幸存者中CD34阳性/谱系标记阴性（CD34(+)Lin(-)）细胞群体中循环HSPCs不同亚型与年龄和辐射相关的变化。我们通过细胞培养列举了功能性HSPC亚型，包括：鹅卵石区域形成细胞；长期培养起始细胞；红系爆式集落形成单位；粒细胞和巨噬细胞集落形成单位；以及T细胞和自然杀伤细胞祖细胞。我们获得了每单位体积血液中每种HSPC亚型的计数以及每种HSPC亚型在CD34(+)Lin(-)细胞中的比例，以代表谱系分化趋势。以性别、年龄和辐射剂量为变量的多因素分析显示，在总的CD34(+)Lin(-)细胞群体和所有HSPC亚型中，计数均随年龄显著下降。至于比例，只有T细胞祖细胞随年龄显著下降，这表明HSPCs向T细胞谱系的分化在一生中随年龄持续下降。然而，无论是CD34(+)Lin(-)细胞群体还是HSPC亚型，在计数或比例上均未显示出显著的辐射诱导剂量依赖性变化。此外，幸存者中HSPC亚型比例之间的相关性恰当地揭示了谱系分化的层次结构。综上所述，我们的研究结果表明，在遭受辐射多年且年龄增长后，在世幸存者中HSPCs的数量和功能总体上可能已恢复到正常水平。
