PXD031548-2

PXD031548 is an original dataset announced via ProteomeXchange.

Title	Brief suppression of SUMOylation in embryonic stem cells generates embryo-like structures
Description	Recent advances in synthetic mammalian embryo models have opened new avenues to understand the complex events controlling lineage specification and morphogenetic processes occurring during peri-implantation and early organogenesis. Two main strategies have been developed to build embryo-like structures (ELSs): by assembling extraembryonic and embryonic stem cells (ESCs) or by subjecting ESCs to various morphogens. Here, we show that mouse ESCs solely exposed to chemical inhibition of SUMOylation, a post-translational modification which acts as a general chromatin barrier to cell fate transitions, generates ELSs comprising both anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs first give rise to adherent spheroids which, once in suspension, self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in an optimized droplet-microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell RNA-sequencing further revealed a variety of cellular lineages including properly positioned anterior neuronal cell types, Schwann cell precursors and paraxial mesoderm segmented into somite-like structures. Mechanistically, transient SUMOylation suppression gradually increases DNA methylation genome-wide and repressive marks deposition at Nanog, enhancing ESC plasticity. Our approach provides a proof of principle for a potential strategy to study early embryogenesis by targeting molecular roadblocks of cell fate change to shape multicellular architecture.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:20.651.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Hendriks
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	sumoylated lysine
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-09 08:03:25	ID requested
1	2023-04-13 07:09:42	announced
⏵ 2	2023-11-14 08:55:21	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: embryo-like structures, repression,SUMO, endogenous, stem cells, spheroids, chromatin

Michael Lund Nielsen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
contact email	ivo.a.hendriks@gmail.com
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/2023/04/PXD031548

PRIDE project URI

• PRIDE
  1. PXD031548
     1. Label: PRIDE project
     2. Name: Brief suppression of SUMOylation in embryonic stem cells generates embryo-like structures