PMID- 27387861 OWN - NLM STAT- MEDLINE DCOM- 20170519 LR - 20181113 IS - 1938-5404 (Electronic) IS - 0033-7587 (Print) IS - 0033-7587 (Linking) VI - 186 IP - 2 DP - 2016 Aug TI - A Molecular Profile of the Endothelial Cell Response to Ionizing Radiation. PG - 141-52 LID - 10.1667/RR14444.1 [doi] AB - Ionizing radiation exposure can cause acute radiation sickness (ARS) by damaging the hematopoietic compartment. Radiation damages quiescent hematopoietic stem cells (HSCs) and proliferating hematopoietic cells, resulting in neutropenia, thrombocytopenia and increased risk for long-term hematopoietic dysfunction and myelodysplasia. While some aspects of the hematopoietic response to radiation injury are intrinsic to hematopoietic cells, the recovery of the HSC pool and overall hematopoiesis is also dependent on signals from bone marrow endothelial cells (BM ECs) within the HSC vascular niche. The precise mechanisms through which BM ECs regulate HSC regeneration remain unclear. Characterization of the altered EC gene expression that occurs in response to radiation could provide a roadmap to the discovery of EC-derived mechanisms that regulate hematopoietic regeneration. Here, we show that 5 Gy total-body irradiation substantially alters the expression of numerous genes in BM ECs within 24 h and this molecular response largely resolves by day 14 postirradiation. Several unique and nonannotated genes, which encode secreted proteins were upregulated and downregulated in ECs in response to radiation. These results highlight the complexity of the molecular response of BM ECs to ionizing radiation and identify several candidate mechanisms that should be prioritized for functional analysis in models of hematopoietic injury and regeneration. FAU - Himburg, Heather A AU - Himburg HA AD - a Division of Hematology/Oncology, Department of Medicine. FAU - Sasine, Joshua AU - Sasine J AD - a Division of Hematology/Oncology, Department of Medicine. FAU - Yan, Xiao AU - Yan X AD - a Division of Hematology/Oncology, Department of Medicine. FAU - Kan, Jenny AU - Kan J AD - a Division of Hematology/Oncology, Department of Medicine. FAU - Dressman, Holly AU - Dressman H AD - d Center for Bioinformatics and Genetics, Duke University, Durham, North Carolina. FAU - Chute, John P AU - Chute JP AD - a Division of Hematology/Oncology, Department of Medicine. AD - b Jonsson Comprehensive Cancer Center and. AD - c Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California; and. LA - eng GR - U01 AI107333/AI/NIAID NIH HHS/United States GR - U19 AI067769/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160707 PL - United States TA - Radiat Res JT - Radiation research JID - 0401245 SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Cell Death/radiation effects MH - Dose-Response Relationship, Radiation MH - Endothelial Cells/*cytology/metabolism/*radiation effects MH - Female MH - Gene Expression Regulation/radiation effects MH - Mice MH - Radiation, Ionizing MH - Time Factors MH - Whole-Body Irradiation/adverse effects PMC - PMC6016841 MID - NIHMS810981 EDAT- 2016/07/09 06:00 MHDA- 2017/05/20 06:00 PMCR- 2018/06/25 CRDT- 2016/07/09 06:00 PHST- 2016/07/09 06:00 [entrez] PHST- 2016/07/09 06:00 [pubmed] PHST- 2017/05/20 06:00 [medline] PHST- 2018/06/25 00:00 [pmc-release] AID - 10.1667/RR14444.1 [doi] PST - ppublish SO - Radiat Res. 2016 Aug;186(2):141-52. doi: 10.1667/RR14444.1. Epub 2016 Jul 7.