PXD016180

PXD016180 is an original dataset announced via ProteomeXchange.

Title	Life-long epigenetic programming of cortical architecture by maternal ‘ Western ’ diet during pregnancy
Description	The evolution of human diets led to preferences towards polyunsaturated fatty acid (PUFA) content with ‘Western’ diets enriched in w-6 PUFA1. Mounting evidence points to w-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans2. When chosen during pregnancy, w-6 PUFA-enriched ‘Western’ diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus2,3. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine w-6 PUFA excess3, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional w-6 PUFA-derived endocannabinoids desensitize CB1 cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity once exposing mouse fetuses to excess w-6 PUFAs in utero. Conversion of w-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB1 cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates with DNA methylome analysis and ATAC-seq uncovering epigenetic reprogramming at >1,400 sites in neurons after prolonged cannabinoid exposure. We find anxiety and depression-like behavioral traits to manifest in adult offspring, which is compatible with genetic models of reduced IgCAM expression to suggest causality to cortical wiring defects4. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit the offsprings’ brain function for life.
HostingRepository	PRIDE
AnnounceDate	2019-11-21
AnnouncementXML	Submission_2019-11-21_03:52:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sally Shirran
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-06 07:52:19	ID requested
⏵ 1	2019-11-21 03:52:05	announced

Cinquina V, Calvigioni D, Farlik M, Halbritter F, Fife-Gernedl V, Shirran SL, Fuszard MA, Botting CH, Poullet P, Piscitelli F, M, á, t, é Z, Szab, ó G, Yanagawa Y, Kasper S, Di Marzo V, Mackie K, McBain CJ, Bock C, Keimpema E, Harkany T, Life-long epigenetic programming of cortical architecture by maternal 'Western' diet during pregnancy. Mol Psychiatry, 25(1):22-36(2020) [pubmed]

submitter keyword: iTRAQ, Epigenetic, Maternal Diet, Fetal Cortex

Tibor Harkany
contact affiliation	Department of Molecular Neurosciences, Center for Brain 1099 Research, Medical University of Vienna, Vienna, Austria
contact email	tibor.harkany@meduniwien.ac.at
lab head
Sally Shirran
contact affiliation	University of St Andrews
contact email	ss101@st-andrews.ac.uk
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/2019/11/PXD016180

PRIDE project URI

• PRIDE
  1. PXD016180
     1. Label: PRIDE project
     2. Name: Life-long epigenetic programming of cortical architecture by maternal ‘ Western ’ diet during pregnancy