Method Profile
A human iPSC-derived multicellular liver-organoid comparison of LIPA-intact and LIPA-deficient tissue, followed by hepatocyte-directed restoration of LIPA expression.
Studying tissue-level lipid-storage and biliary responses and measuring molecular rescue after a proposed gene-restoration intervention.
Isogenic LIPA-intact and LIPA-deficient human iPSC-derived liver organoids containing hepatocyte-like, biliary-like and stromal populations.
Matched genotype comparison and hepatocyte-directed LIPA restoration in the deficient organoids; independent differentiation experiments supplied the principal molecular comparisons.
Disease model and comparator
LIPA-deficient organoids compared with isogenic LIPA-intact organoids.
Restoration condition
LIPA expression restored preferentially in hepatocyte-like cells of the deficient organoids.
Compare genotype-specific tissue and cell-state responses; interpret the pooled single-cell dataset alongside molecular results from separate differentiation experiments and the isolated biliary-organoid contrast.
Isogenic mutant/control organoids, separate isolated biliary cultures, and hepatocyte-directed LIPA restoration.
Single-cell RNA sequencing used one pooled organoid sample per genotype; quantitative molecular assays used independent differentiation experiments (typically 4–7 for restoration figures).
LIPA-intact organoids, untreated LIPA-deficient organoids and isolated biliary-organoid observations.
Mutant multicellular organoids showed lipid accumulation, elevated inflammatory and fibrogenic gene expression, and a biliary response; restored LIPA attenuated the reported disease-associated molecular programs. Isolated biliary cultures did not reproduce the ductular-reaction program.
Isogenic human liver organoids with LIPA loss reproduced lipid accumulation and multicellular inflammatory and biliary responses with increased fibrogenic gene expression. Restoring LIPA in hepatocyte-like cells attenuated these molecular signals.
