Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors

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

doi:10.1667/RR14209.1

Title: Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors

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Abstract

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 themore »« less

Authors:

Kyoizumi, Seishi ^[1]; Kubo, Yoshiko ^[1]; Misumi, Munechika ^[2]; Kajimura, Junko ^[1]; Yoshida, Kengo ^[1]; Hayashi, Tomonori ^[1]; Imai, Kazue ^[1]; Ohishi, Waka ^[3]; Nakachi, Kei ^[1]; Young, Lauren F. ^[4]; Shieh, Jae-Hung ^[5]; Moore, Malcolm A. ^[5]; van den Brink, Marcel R. M. ^[4]; Kusunoki, Yoichiro ^[1]

Radiation Effects Research Foundation, Hiroshima (Japan).
Radiation Effects Research Foundation, Hiroshima (Japan). Dept. of Statistics
Radiation Effects Research Foundation, Hiroshima (Japan). Dept. of Clinical Studies
Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Medicine and Immunology
Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Cell Biology Program

Publication Date:: Thu Dec 31 00:00:00 EST 2015

Research Org.:: National Academy of Sciences, Washington, DC (United States)

Sponsoring Org.:: USDOE; National Institutes of Health (NIH)

OSTI Identifier:: 1467450

Grant/Contract Number:: HS0000031; HHSN272200900059C

Resource Type:: Accepted Manuscript

Journal Name:: Radiation Research

Additional Journal Information:: Journal Volume: 185; Journal Issue: 1; Journal ID: ISSN 0033-7587

Publisher:: Radiation Research Society

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats


                    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., and Kusunoki, Yoichiro. Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.  United States: N. p., 2015. 
Web.  doi:10.1667/RR14209.1.

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                    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. Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.  United States.  https://doi.org/10.1667/RR14209.1

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                    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., and Kusunoki, Yoichiro. Thu .  
"Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors".  United States.  https://doi.org/10.1667/RR14209.1.  https://www.osti.gov/servlets/purl/1467450.

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@article{osti_1467450,

  title        = {Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors},

  author       = {Kyoizumi, Seishi and Kubo, Yoshiko and Misumi, Munechika and Kajimura, Junko and Yoshida, Kengo and Hayashi, Tomonori and Imai, Kazue and Ohishi, Waka and Nakachi, Kei and Young, Lauren F. and Shieh, Jae-Hung and Moore, Malcolm A. and van den Brink, Marcel R.  M. and Kusunoki, Yoichiro},

  abstractNote = {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. In conclusion, 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.},

  doi          = {10.1667/RR14209.1},

  journal      = {Radiation Research},

  number       = 1,

  volume       = 185,

  place        = {United States},

  year         = {Thu Dec 31 00:00:00 EST 2015},

  month        = {Thu Dec 31 00:00:00 EST 2015}

}

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