PXD002339-1

PXD002339 is an original dataset announced via ProteomeXchange.

Title	Cytoplasmic erythrocyte proteome in Diamond Blackfan Anemia
Description	Diamond Blackfan Anemia (DBA) is a rare, congenital erythrocyte aplasia that is usually caused by haploinsufficiency of ribosomal proteins due to diverse mutations in one of several ribosomal protein genes. A striking feature of this disease is that a range of different mutations in ribosomal proteins results in similar disease phenotypes primarily characterized by erythrocyte abnormalities and macrocytic anemia, while most other cell types are minimally affected. Previously, we analyzed the erythrocyte membrane proteomes of several DBA patients and identified several proteins that are not typically associated with this cell type that suggested inflammatory mechanisms contribute to the pathogenesis of DBA. In this study, we evaluated the erythrocyte cytosolic proteome of DBA patients through in-depth analysis of hemoglobin-depleted erythrocyte cytosol. The simple, reproducible, hemoglobin depletion using nickel columns enabled in-depth analysis of over 1000 cytosolic erythrocyte proteins with minimal subsequent fractionation of the proteome. Label-free quantitation and statistical analysis identified 29 proteins that were significantly changed in DBA patients compared to matched healthy control donors. Some of the proteins that were significantly increased in DBA erythrocyte cytoplasm included three proteasome subunit beta proteins that make up the immunoproteasome and proteins induced by interferon-γ such as n-myc interactor and interferon-induced 25 kDa protein [NMI and IFI35 respectively]. Pathway analysis confirmed the presence of an inflammatory signature with erythrocytes of DBA patients and predicted key upstream regulators including mitogen activated kinase 1, interferon-γ, tumor suppressor p53, and tumor necrosis factor. These results show that erythrocytes in DBA patients are intrinsically different from those in healthy controls which may be due to an inflammatory response resulting from the inherent molecular defect of ribosomal protein haploinsufficiency or changes in the bone marrow microenvironment that leads to red cell aplasia in DBA patients.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_09:58:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Esther Pesciotta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-06-09 01:23:40	ID requested
⏵ 1	2018-10-24 09:58:43	announced
2	2024-10-22 04:09:24	announced	2024-10-22: Updated project metadata.

Pesciotta EN, Lam HS, Kossenkov A, Ge J, Showe LC, Mason PJ, Bessler M, Speicher DW, In-Depth, Label-Free Analysis of the Erythrocyte Cytoplasmic Proteome in Diamond Blackfan Anemia Identifies a Unique Inflammatory Signature. PLoS One, 10(10):e0140036(2015) [pubmed]

submitter keyword: Human, erythrocyte, LC-MS/MS

David W. Speicher
contact affiliation	The Wistar Institute Philadelphia, PA USA
contact email	speicher@wistar.org
lab head
Esther Pesciotta
contact affiliation	The Children's Hospital of Philadelphia
contact email	esther.pesciotta@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002339
     1. Label: PRIDE project
     2. Name: Cytoplasmic erythrocyte proteome in Diamond Blackfan Anemia