PXD057003

PXD057003 is an original dataset announced via ProteomeXchange.

Title	Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival
Description	Proper control of inflammatory responses is essential for embryonic development, but the underlying mechanism is poorly understood. Here, we show that under physiological conditions, inactivation of ISG15, an inflammation amplifier, is associated with the interaction of Beclin 1 (Becn1), via its ECD domain, with STAT3 in the major fetal hematopoietic organ of mice. Conditional loss of Becn1 caused sequential dysfunction and exhaustion of fetal liver hematopoietic stem cells, leading to lethal inflammatory cell-biased hematopoiesis in the fetus. Molecularly, the absence of Becn1 resulted in the release of STAT3 from Becn1 tethering and subsequent phosphorylation and translocation to the nucleus, which in turn directly activated the transcription of ISG15 in fetal liver hematopoietic cells, coupled with increased ISGylation and production of inflammatory cytokines, whereas inactivating STAT3 reduced ISG15 transcription and inflammation but improved hematopoiesis potential, and further silencing ISG15 mitigated the above collapse in the Becn1 null hematopoietic lineage. The Becn1-STAT3-ISG15 axis remains functional in Atg5/7-disrupted fetal hematopoietic organs. These results suggest that Becn1, in an autophagy-independent manner, secures hematopoiesis and survival of the fetus by directly inhibiting STAT3-ISG15 activation to prevent cytokine storms. Our findings highlight a previously undocumented role of Becn1 in governing ISG15 to safeguard the fetus.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_04:05:50.122.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yixuan Fang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-21 02:37:10	ID requested
⏵ 1	2025-05-07 04:05:51	announced

Wei W, Gao X, Qian J, Li L, Zhao C, Xu L, Zhu Y, Liu Z, Liu N, Wang X, Jin Z, Liu B, Xu L, Dong J, Zhang S, Wang J, Zhang Y, Yu Y, Yan Z, Yang Y, Lu J, Fang Y, Yuan N, Wang J, Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival. J Clin Invest, 135(3):(2025) [pubmed]

10.1172/jci177375;

submitter keyword: Beclin 1,Mouse, Fetal liver

Jianrong Wang
contact affiliation	Research Center for Blood Engineering and Manufacturing, Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.
contact email	jrwang@suda.edu.cn
lab head
Yixuan Fang
contact affiliation	Soochow university
contact email	yxfang@suda.edu.cn
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/PXD057003

PRIDE project URI

• PRIDE
  1. PXD057003
     1. Label: PRIDE project
     2. Name: Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival