PXD068917

PXD068917 is an original dataset announced via ProteomeXchange.

Title	Promoting Astrocyte-Neuron Triiodothyronine Shuttling Attenuates Brain Damage in Neonatal Hypoxic-Ischemic Encephalopathy
Description	Background: Neonatal Hypoxic-Ischemic Encephalopathy (HIE) is a critical lifelong disabling neonatal disease with insufficient effective therapies. Signaling molecules derived from astrocyte-neuron crosstalk have the potential to improve improve the prognosis, but relevant HIE research is limited. Methods: Rice-Vannucci model-induced hypoxic-ischemic brain damage (HIBD) in postnatal day 7 (P7) rat pups was confirmed by Pathological staining and laser speckle imaging. P10 whole brains underwent single-cell RNA sequencing, astrocytes after oxygen-glucose deprivation had proteomic sequencing. Multiplex immunofluorescence identified astrocyte subtypes; Enzyme-linked immunosorbent assay and Western blotting detected thyroid hormones and signaling pathways. Therapeutic efficacy was evaluated by Pathological staining and Morris Water Maze. Results: Utilizing a comprehensive single-cell transcriptomic atlas of the entire brain, this study elucidates a significant transcriptional association between astrocytes and neurons. We identified five distinct astrocyte subpopulations and characterized the Dio2⁺Slc1a2⁺subpopulation as "Metabo-neuroprotective Astrocytes" through multi-dimensional evidence. Notably, the abundance of this subpopulation was markedly diminished in the HIBD model. Pseudotime analysis further demonstrated that astrocytic proinflammatory activity is temporally regulated. Both in vivo and in vitro experiments corroborated that enhancing Dio2 expression in astrocytes or the exogenous administration of triiodothyronine (T3) can facilitate neural repair and ameliorate behavioral outcomes during both the acute and long-term phases following HIBD. Conclusions: A novel astrocyte subpopulation with neuroprotective effects was identified in the HIE model, and the temporal heterogeneity of its proinflammatory response was revealed. Meanwhile, a new crosstalk mechanism mediated by T3 shuttling between astrocytes and neurons was discovered, which can alleviate HIBD.
HostingRepository	iProX
AnnounceDate	2025-09-27
AnnouncementXML	Submission_2025-09-28_18:08:44.707.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	GuoSheng Yu
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-28 18:08:21	ID requested
⏵ 1	2025-09-28 18:08:45	announced

Dataset with its publication pending

submitter keyword: HIE, Astrocyte, Astrocyte-neuron crosstalk, T3, scRNA-seq

ZhenLang Lin
contact affiliation	Second Clinical Medical College, Wenzhou Medical University
contact email	yuguosheng1997@163.com
lab head
GuoSheng Yu
contact affiliation	Second Clinical Medical College, Wenzhou Medical University
contact email	yuguosheng1997@163.com
dataset submitter

iProX dataset URI