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PXD006701

PXD006701 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe role of HIF1 in enhancing radio resistance of mouse MSCs
DescriptionMesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSC have an efficient DNA damage response (DDR) and are consequently reatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif is involved in MSC radio-resistance, however its exact mechanism of action remains unknown. In order to dissect the involvement of Hif-1α in the DDR, we have generated using CRISPR/Cas9 technology, a stable MS5 mouse MSC cell line lacking Hif-1 expression. Herein, we show that it is the whole Hif-1 transcription factor, and not only the Hif-1α subunit, that modulates the DDR of mouse MSCs, and that this effect is dependent upon the integrity of the DNA binding domain. We have also characterized the Hif-1α-dependent proteomic changes undergone by hypoxic MS5 cells. These findings have important implications for the modulation of MSC radio-resistance in the context of BMT and cancer.
HostingRepositoryPRIDE
AnnounceDate2018-05-16
AnnouncementXMLSubmission_2018-05-16_02:01:06.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEugene Dillon
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; iodoacetic acid derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-06-12 07:52:57ID requested
12018-05-16 02:01:07announced
Publication List
Calvo-Asensio I, Dillon ET, Lowndes NF, Ceredig R, The Transcription Factor Hif-1 Enhances the Radio-Resistance of Mouse MSCs. Front Physiol, 9():439(2018) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Mesenchymal stromal cells, DNA damage response, ionizing radiation, hypoxia, label-free proteomics
Contact List
Rhodri Ceredig
contact affiliationRhodri Ceredig, Professor of Immunology, Discipline of Physiology, College of Medicine & Nursing Health Science, Room 217 Orbsen Building National University of Ireland, Galway H91 DK59
contact emailrhodri.ceredig@nuigalway.ie
lab head
Eugene Dillon
contact affiliationUCD
contact emaileugene.dillon@ucd.ie
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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