PXD064617

PXD064617 is an original dataset announced via ProteomeXchange.

Title	Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets
Description	Generating stem cell-derived glucagon-producing α and insulin-producing β cells allows to engineer in vitro biomimetics of the islet of Langerhans, the micro-organ controlling blood glucose; however, there is still a major knowledge gap in the mechanism by which human stem cell-derived α and β cells are specified. Mouse studies postulated that Aristaless Related homeobox (Arx) and Paired box 4 (Pax4) transcription factors cross-inhibit each other in endocrine progenitors to promote α or β cell fate allocation, respectively. To test this model in human, we generated an ARXCFP/CFP; PAX4mCherry/mCherry double knock-in reporter induced pluripotent stem cell line to combine time-resolved cell lineage labeling with high-resolution single cell multiomic analysis. Strikingly, lineage labelling and tracing, proteomic and gene regulatory network analysis and potency assays revealed a human specific regulation of α versus β cell fate allocation. Pharmacological perturbation using drugs previously proposed to trigger α-to-β cell transdifferentiation or identified via our gene regulatory network analysis led to enhanced endocrine induction and directed α versus β cell fate commitment. Thus, shedding light on basic mechanisms of endocrine induction and fate segregation not only paves the way to engineer islets from pluripotent stem cells, but has broader implications for cell-replacement therapy, disease modelling and drug screening.
HostingRepository	PRIDE
AnnounceDate	2026-05-19
AnnouncementXML	Submission_2026-05-19_05:15:50.889.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juliane Merl-Pham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 04:03:24	ID requested
⏵ 1	2026-05-19 05:15:51	announced

Dataset with its publication pending

submitter keyword: LC-MSMS

Heiko Lickert
contact affiliation	Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Neuherberg, Germany; School of Medicine, Technical University of Munich, Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
contact email	heiko.lickert@helmholtz-munich.de
lab head
Juliane Merl-Pham
contact affiliation	Metabolomics and Proteomics Core, Helmholtz Munich
contact email	juliane.merl@helmholtz-muenchen.de
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/2026/05/PXD064617

PRIDE project URI

• PRIDE
  1. PXD064617
     1. Label: PRIDE project
     2. Name: Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets