Single cell RNAseq (cTEC sort) dataset

Abstract: Family of Sequence Similarity 83H (FAM83H/ SACK1H) is primarily expressed in epithelial cells, where it is associated with CK1 and keratins to regulate cytoskeletal organization, cell proliferation, and vesicular trafficking. Mutations in FAM83H cause amelogenesis imperfecta (AI), suggesting its critical role in enamel formation. We generated Fam83h-deficient mice (Fam83hem2(IMPC)Ccpcz, Fam83h-/-) and mice lacking a part of N-terminal CK1-binding domain (Fam83h∆87/∆87). Consistent with other Fam83h-deficient models, these mice are subviable, smaller in size, and display a sparse, scruffy coat, scaly skin, weakness, and hypoactivity. Importantly, both strains exhibit impaired lymphoid cell production during early postnatal development. In the thymus, Fam83h expression is restricted to thymic epithelial cells (TECs), and its deficiency in stromal cells results in disrupted thymic architecture and severe impairment of DN3 (double-negative) T cell expansion, ultimately leading to insufficient T cell production. Single-cell transcriptomic analysis has shown that Fam83h-/- cTECs express lower levels of TEC master regulator Foxn1, along with its multiple target genes. This suggests a role for FAM83H and CK1 in cTEC maturation.