PXD062322

PXD062322 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics and Proteomics of wild-type and TauT-/- leukemia cells
Description	Signals from the microenvironment are known to be critical for development, sustaining adult stem cells, and for oncogenic progression. While candidate niche-driven signals that can promote cancer progression have been identified, concerted efforts to comprehensively map microenvironmental ligands for cancer stem cell specific surface receptors have been lacking. Here, we use temporal single cell RNA-sequencing to identify molecular cues from the bone marrow stromal niche that engage leukemia stem cells (LSC) during oncogenic progression. We integrate these data with our RNA-seq analysis of human LSCs from distinct aggressive myeloid cancer subtypes and our CRISPR based in vivo LSC dependency map7 to develop a temporal receptor-ligand interactome essential for disease progression. These analyses identify the taurine transporter (TauT)-taurine axis as a critical dependency of myeloid malignancies. We show that taurine production is restricted to the osteolineage population during cancer initiation and expansion. Inhibiting taurine synthesis in osteolineage cells impairs LSC growth in vitro and improves survival outcomes in vivo. Using TauT genetic loss of function murine models and patient-derived AML cells, we show that TauT inhibition significantly impairs in vivo myeloid leukemia progression. Consistent with elevated TauT expression in venetoclax resistant AML, TauT inhibition synergizes with venetoclax to block growth of primary human AML cells. Mechanistically, our metabolomic, proteomic and transcriptomic approaches indicate that loss of taurine uptake inhibits Rag-GTP dependent mTOR activation and downstream glycolytic metabolism. Collectively, our work establishes the temporal landscape of stromal signals during leukemia progression and identifies taurine as an important regulator of myeloid malignancies.
HostingRepository	PRIDE
AnnounceDate	2025-03-28
AnnouncementXML	Submission_2025-03-28_09:36:50.329.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kyle Swovick
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-27 11:57:59	ID requested
⏵ 1	2025-03-28 09:36:50	announced

Dataset with its publication pending

submitter keyword: Human, cancer, proteomics, taurine, leukemia, phospho-proteomics

Jeevisha Bajaj
contact affiliation	Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA
contact email	Jeevisha_Bajaj@URMC.Rochester.edu
lab head
Kyle Swovick
contact affiliation	University of Rochester Medical Center Mass Spectrometry Shared Resource Laboratory
contact email	kswovick@ur.rochester.edu
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/2025/03/PXD062322

PRIDE project URI

• PRIDE
  1. PXD062322
     1. Label: PRIDE project
     2. Name: Phosphoproteomics and Proteomics of wild-type and TauT-/- leukemia cells