Method Profile
Structured human skin organoids connect fibroblast-state analysis with a tissue-level RUNX2 response to a candidate compound.
Investigation of fibrotic stromal states and follow-up testing of candidates identified in human fibroblast assays.
iPSC-derived skin organoids with epidermal and dermal-like compartments; two independent iPSC-derived organoid lines were used for the drug-associated RUNX2 comparison.
TGF-β-induced fibrotic remodeling followed by F0565-0303 exposure; organoid immunofluorescence is interpreted separately from fibroblast and mouse experiments.
Human skin model
Mature iPSC-derived skin organoids with untreated and TGF-β-stimulated comparison conditions.
Molecular measurements
RUNX2 staining and spatial analysis; related single-cell data characterize fibroblast populations.
Compare the tissue RUNX2 signal under matched stimulation and candidate-treatment conditions. Keep the thirteen-compound primary-fibroblast screen as a separate experiment.
Apply F0565-0303 after fibrosis-associated changes are established and quantify RUNX2 immunofluorescence.
Two independent iPSC-derived organoid lines; reported imaging uses three organoids per condition with sampled regions.
TGF-β-stimulated organoids with or without the candidate; untreated tissue provides a model reference.
F0565-0303 reduced organoid RUNX2 signal. Primary-cell protein/transcript and mouse histology findings provide separate supporting evidence.
A preprint combines human skin organoids, fibroblast perturbation and compound screening to investigate RUNX2-associated fibrosis. The candidate F0565-0303 reduced RUNX2 staining in organoids, while additional assays examined its effects in fibroblasts and mice.
