PXD027331

PXD027331 is an original dataset announced via ProteomeXchange.

Title	Global Identification of the miR-130a targetome in human HSPC Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML
Description	Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells have firmly established the existence of shared core stemness properties. However, the discordance between mRNA and protein signatures underscores an important role for post-transcriptional regulation by miRNAs in governing this critical nexus. Here, we identify miR-130a as a regulator of hematopoietic stem cell (HSC) self-renewal and lineage differentiation. Integration of mass spectrometry and chimeric AGO2 eCLIP-seq identify TBL1XR1 as a primary miR-130a target. TBL1XR1 loss of function impairs lymphoid differentiation and expands long-term (LT)-HSC. This post-transcriptional regulation by miR-130a is usurped in t(8;21) acute myeloid leukemia (AML). Reduction of miR-130a levels in t(8;21) AML cells results in altered chromatin binding and composition of the AML1-ETO complex, demonstrating that miR-130a is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Our study establishes that comprehensive identification of the miRNA targetome within primary tissue enables the discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:46:38.792.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erwin Schoof
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-15 09:28:59	ID requested
1	2024-06-22 09:11:11	announced
⏵ 2	2024-10-22 06:46:39	announced	2024-10-22: Updated project metadata.

Krivdova G, Voisin V, Schoof EM, Marhon SA, Murison A, McLeod JL, Gabra MM, Zeng AGX, Aigner S, Yee BA, Shishkin AA, Van Nostrand EL, Hermans KG, Trotman-Grant AC, Mbong N, Kennedy JA, Gan OI, Wagenblast E, De Carvalho DD, Salmena L, Minden MD, Bader GD, Yeo GW, Dick JE, Lechman ER, Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML. Cell Rep, 38(10):110481(2022) [pubmed]

10.1016/j.celrep.2022.110481;

submitter keyword: LC-MS, acute myeloid leukemia,miRNA, hematopoiesis

John Dick
contact affiliation	1 Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada 2 Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A5, Canada
contact email	jdick@uhnresearch.ca
lab head
Erwin Schoof
contact affiliation	Technical University of Denmark
contact email	erws@dtu.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD027331

PRIDE project URI

• PRIDE
  1. PXD027331
     1. Label: PRIDE project
     2. Name: Global Identification of the miR-130a targetome in human HSPC Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML