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Spatial profiling of hypoxic injury in human kidney organoids

ABSTRACT: This dataset relates to a spatial transcriptomic experiment investigating potential reparative and inflammatory roles for macrophages in human iPSC-derived kidney organoids exposed to hypoxic injury, linked to a broader study of ischaemic kidney injury and repair in this model (https://doi.org/10.1101/2023.10.04.558359). Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischaemia is a leading cause of AKI, where reduced blood flow to the kidney triggers hypoxia and cell death in the nephron epithelium, impairing essential fluid handling and waste removal functions. While injured tubules have some capacity to recover, severe injury can result in chronic kidney disease (CKD) through a maladaptive repair process characterised by failed epithelial regeneration, inflammation, and metabolic dysregulation. Immune cells critically influence kidney injury responses in vivo, with tissue-resident macrophages driving either repair or harmful inflammation, fibrosis, and progression to CKD. To complement prior bulk RNAseq analysis and investigate the role of macrophages in AKI and maladaptive repair within the tissue microenvironment, we integrated iPSC-derived macrophages into kidney organoids and investigated their response to hypoxic injury and effect on the surrounding tissue with spatial transcriptomics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307588 | GEO | 2026/06/26

REPOSITORIES: GEO

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Hypoxic injury triggers maladaptive repair in human kidney organoids

Project 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.

2026-06-26 | PXD042882 | Pride

Hypoxic injury triggers maladaptive repair in human kidney organoids

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Hypoxic injury triggers maladaptive repair in human kidney organoids [scRNA-seq]

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Hypoxic injury triggers maladaptive repair in human kidney organoids

Project description:Hypoxic injury triggers maladaptive repair in human kidney organoids

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Hypoxic injury triggers maladaptive repair in human kidney organoids

Project description:Hypoxic injury triggers maladaptive repair in human kidney organoids

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Cyclo (His-Pro) is an effective treatment for the AKI-to-CKD Transition

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Hypoxic injury triggers maladaptive repair in human kidney organoids [scRNA-seq]

Project description:Hypoxic injury triggers maladaptive repair in human kidney organoids [scRNA-seq]

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