PXD042882-1

PXD042882 is an original dataset announced via ProteomeXchange.

Title	Hypoxic injury triggers maladaptive repair in human kidney organoids
Description	Reduction in blood supply to the kidneys occurs to certain extent during kidney injury (AKI). Individuals who suffered AKI are at risk of developing chronic kidney disease (CKD) through a maladaptive repair process. At present, no therapies exist to prevent the AKI to CKD transition. Here, we present a human kidney organoid model of AKI and maladaptive regeneration. Organoids were generated from human induced pluripotent stem cells and cultured in hypoxic or normoxic conditions from days 18-20 of differentiation. Organoids were collected at day 20 to assess hypoxic injury, and after a 5-day recovery in normoxic conditions to assess maladaptive repair. The transcriptome, proteome and metabolome were profiled. Gene expression analysis of day 20 hypoxic organoids identified signatures of injury, cell death (necroptosis and ferroptosis), cell cycle arrest and changes in metabolism. The maladaptive repair phenotype was supported by enrichment of pathways associated with inflammatory signals, oxidative stress, and tissue remodelling. Specific genes associated with kidney injury and disease such as GDF15, MMP7, ICAM1, TGFB1, CCN1, C3 and S100A8/9 were upregulated. Single-cell RNA sequencing localised expression of maladaptive repair genes and activation of TNF and JAK-STAT signalling pathways specific to tubular epithelial cells. Dysregulation in metabolic pathways such as glycolysis and gluconeogenesis, amino acid and lipid metabolisms were conserved in this model. Therefore, these results support the use of kidney organoids as a model of AKI and early CKD that can be used for biomarker validation, elucidation of pathological mechanisms, and drug screening.
HostingRepository	PRIDE
AnnounceDate	2026-06-26
AnnouncementXML	Submission_2026-06-26_02:37:11.919.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joel Steele
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-11 19:37:11	ID requested
⏵ 1	2026-06-26 02:37:12	announced

Dataset with its publication pending

submitter keyword: Acute kidney Injury, Metabolomics, Organoids, Chronic Kidney Disease, Transcriptomics, Maladaptive Regeneration, Proteomics, Hypoxia

Ana B Nunez-Nescolarde
contact affiliation	Department of Anatomy and Developmental BiologyMonash University, Clayton, Victoria, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. Alexander N Combes alex.combes@monash.edu. David J Nikolic-Paterson david.nikolic-paterson@monash.edu.
contact email	Ana.nuneznescolarde@monash.edu
lab head
Joel Steele
contact affiliation	Monash
contact email	joel.steele@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042882
     1. Label: PRIDE project
     2. Name: Hypoxic injury triggers maladaptive repair in human kidney organoids