Mesenchymal Cell Replacement Corrects Thymic Hypoplasia in Murine Models of 22q11.2 Deletion Syndrome

The study investigated thymic hypoplasia in 22q11.2 deletion syndrome (22q11.2DS) using mouse models, revealing that the condition was linked to mesenchymal cell dysfunction. Despite similar proportions of cell types in embryonic thymuses of 22q11.2DS models and controls, the thymuses were growth-restricted. Replacing the defective mesenchymal cells with normal ones restored tissue growth. Single-cell RNA-Seq identified 17 cell subsets, with significant transcriptome differences in the mesenchymal subsets, particularly affecting extracellular matrix proteins and leading to increased collagen deposition. Treatment with minoxidil, which attenuates collagen cross-links, improved thymic tissue expansion. The study concluded that mesenchymal cells were responsible for the thymic hypoplasia in 22q11.2DS mouse models, and normal mesenchyme substitution corrected the defect.