PXD052342

PXD052342 is an original dataset announced via ProteomeXchange.

Title	TFEB controls syncytiotrophoblast formation and hormones production in placenta
Description	TFEB, a bHLH-leucine zipper transcription factor belonging to the MiT/TFE family, globally modulates cell metabolism by regulating autophagy and lysosomal functions. Remarkably, loss of TFEB in mice causes embryonic lethality due to severe defects in placentation associated with aberrant vascularization and resulting hypoxia. However, the molecular mechanism underlying this phenotype has remained elusive. By integrating multi-omics approaches with functional assays, we have uncovered an unprecedented function for TFEB in promoting the formation of a functional syncytiotrophoblast in the placenta. Our findings demonstrate that syncytiotrophoblast formation is marked by TFEB nuclear translocation and binding to the promoters of crucial placental genes, including genes encoding fusogenic proteins (Syncytin-1 and Syncythin-2) and enzymes involved in steroidogenic pathways, such as CYP19A1, the rate-limiting enzyme for the synthesis of 17β-Estradiol (E2). Conversely, TFEB depletion impairs both syncytial fusion and endocrine properties of syncytiotrophoblast, as demonstrated by a significant decrease in the secretion of placental hormones and E2 production. Notably, restoration of TFEB expression resets syncytiotrophoblast identity. Our findings identify that TFEB controls placental development and function by orchestrating both the transcriptional program underlying trophoblast fusion and the acquisition of endocrine function, which are crucial for the bioenergetic requirements of embryonic development.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_17:15:14.858.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcella Cesana
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-17 05:48:15	ID requested
⏵ 1	2025-05-06 17:15:15	announced

10.1038/s41418-024-01337-y;

Cesana M, Tufano G, Panariello F, Zampelli N, Soldati C, Mutarelli M, Montefusco S, Grieco G, Sepe LV, Rossi B, Nusco E, Rossignoli G, Panebianco G, Merciai F, Salviati E, Sommella EM, Campiglia P, Martello G, Cacchiarelli D, Medina DL, Ballabio A, TFEB controls syncytiotrophoblast formation and hormone production in placenta. Cell Death Differ, 31(11):1439-1451(2024) [pubmed]

submitter keyword: suncytiotrophoblast,TFEB, placenta

Marcella Cesana
contact affiliation	TIGEM
contact email	m.cesana@tigem.it
lab head
Marcella Cesana
contact affiliation	TIGEM
contact email	m.cesana@tigem.it
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/2025/05/PXD052342

PRIDE project URI

• PRIDE
  1. PXD052342
     1. Label: PRIDE project
     2. Name: TFEB controls syncytiotrophoblast formation and hormones production in placenta