Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

Sanket S. Acharya, Wojciech Fendler, Jacqueline Watson, Abigail Hamilton, Yunfeng Pan, Emily Gaudiano, Patryk Moskwa, Payel Bhanja, Subhrajit Saha, Chandan Guha, Kalindi Parmar, Dipanjan Chowdhury

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.

Original languageEnglish (US)
JournalScience Translational Medicine
Volume7
Issue number287
DOIs
StatePublished - May 13 2015

Fingerprint

MicroRNAs
Radiation
Survival
Wounds and Injuries
Serum
Hematopoietic Stem Cells
Radiation Injuries
Whole-Body Irradiation
Radiation-Protective Agents
Radioactive Hazard Release
Hematopoietic System
Radiation Dosage
Health
Bone Marrow Cells
Biomarkers

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Acharya, S. S., Fendler, W., Watson, J., Hamilton, A., Pan, Y., Gaudiano, E., ... Chowdhury, D. (2015). Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury. Science Translational Medicine, 7(287). https://doi.org/10.1126/scitranslmed.aaa6593

Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury. / Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan.

In: Science Translational Medicine, Vol. 7, No. 287, 13.05.2015.

Research output: Contribution to journalArticle

Acharya, SS, Fendler, W, Watson, J, Hamilton, A, Pan, Y, Gaudiano, E, Moskwa, P, Bhanja, P, Saha, S, Guha, C, Parmar, K & Chowdhury, D 2015, 'Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury', Science Translational Medicine, vol. 7, no. 287. https://doi.org/10.1126/scitranslmed.aaa6593
Acharya, Sanket S. ; Fendler, Wojciech ; Watson, Jacqueline ; Hamilton, Abigail ; Pan, Yunfeng ; Gaudiano, Emily ; Moskwa, Patryk ; Bhanja, Payel ; Saha, Subhrajit ; Guha, Chandan ; Parmar, Kalindi ; Chowdhury, Dipanjan. / Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury. In: Science Translational Medicine. 2015 ; Vol. 7, No. 287.
@article{ab40d7a14f064001af0c8ba43d256315,
title = "Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury",
abstract = "Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.",
author = "Acharya, {Sanket S.} and Wojciech Fendler and Jacqueline Watson and Abigail Hamilton and Yunfeng Pan and Emily Gaudiano and Patryk Moskwa and Payel Bhanja and Subhrajit Saha and Chandan Guha and Kalindi Parmar and Dipanjan Chowdhury",
year = "2015",
month = "5",
day = "13",
doi = "10.1126/scitranslmed.aaa6593",
language = "English (US)",
volume = "7",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "287",

}

TY - JOUR

T1 - Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

AU - Acharya, Sanket S.

AU - Fendler, Wojciech

AU - Watson, Jacqueline

AU - Hamilton, Abigail

AU - Pan, Yunfeng

AU - Gaudiano, Emily

AU - Moskwa, Patryk

AU - Bhanja, Payel

AU - Saha, Subhrajit

AU - Guha, Chandan

AU - Parmar, Kalindi

AU - Chowdhury, Dipanjan

PY - 2015/5/13

Y1 - 2015/5/13

N2 - Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.

AB - Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation.

UR - http://www.scopus.com/inward/record.url?scp=84929650594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929650594&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aaa6593

DO - 10.1126/scitranslmed.aaa6593

M3 - Article

C2 - 25972001

AN - SCOPUS:84929650594

VL - 7

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 287

ER -