PXD018887-1

PXD018887 is an original dataset announced via ProteomeXchange.

Title	Mutations and variants of ONECUT1 in diabetes
Description	Genes involved in distinct diabetes types suggest shared disease mechanisms. We show that rare ONECUT1 coding variants cause monogenic recessive diabetes (neonatal or very early-onset, syndromic) in two unrelated patients, and monogenic dominant diabetes (early adult-onset) in heterozygous relatives of these and 13 additional unrelated cases. Patients heterozygous for rare ONECUT1 coding variants define a subgroup of T2D with early-onset diabetes and other features. In addition, common regulatory ONECUT1 variants are associated with multifactorial T2D. Directed differentiation of human pluripotent stem cells to the pancreatic lineage revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. We uncovered that ONECUT1 activates the pro-endocrine genes NKX6.1 and NKX2.2 through binding to their cis-regulatory elements. Globally, ONECUT1-directed gene transcription occurs in association with major islet transcription factors, at clusters of pancreas- and endocrine-specific enhancers within open chromatin. ONECUT1 regulates a transcriptional and epigenetic machinery critical for proper endocrine pancreatic development, involved in a spectrum of diabetes, monogenic recessive and dominant, and multifactorial.
HostingRepository	PRIDE
AnnounceDate	2021-11-03
AnnouncementXML	Submission_2021-11-03_07:43:17.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Krumm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-29 01:03:55	ID requested
⏵ 1	2021-11-03 07:43:18	announced

Philippi A, Heller S, Costa IG, Sen, é, e V, Breunig M, Li Z, Kwon G, Russell R, Illing A, Lin Q, Hohwieler M, Degavre A, Zalloua P, Liebau S, Schuster M, Krumm J, Zhang X, Geusz R, Benthuysen JR, Wang A, Chiou J, Gaulton K, Neubauer H, Simon E, Klein T, Wagner M, Nair G, Besse C, Dandine-Roulland C, Olaso R, Deleuze JF, Kuster B, Hebrok M, Seufferlein T, Sander M, Boehm BO, Oswald F, Nicolino M, Julier C, Kleger A, Mutations and variants of ONECUT1 in diabetes. Nat Med, 27(11):1928-1940(2021) [pubmed]

submitter keyword: differentiation, stem cells,Onecut1, Proteomics

Bernhard Kuster
contact affiliation	Chair of Proteomics and Bioanalytics, TU Munich
contact email	kuster@tum.de
lab head
Johannes Krumm
contact affiliation	Chair of Proteomics and Bioanalytics, TU Munich
contact email	johannes.krumm@tum.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/2021/11/PXD018887

PRIDE project URI

• PRIDE
  1. PXD018887
     1. Label: PRIDE project
     2. Name: Mutations and variants of ONECUT1 in diabetes