Although spinal muscular atrophy (SMA) is a motor neuron disease caused by the loss of survival of motor neuron (SMN) proteins, there is growing evidence that non-neuronal cells play important roles in SMA pathogenesis. However, transcriptome alterations occurring at the single-cell level in SMA spinal cord remain unknown, preventing us from fully comprehending the role of specific cells. Here, we performed single-cell RNA sequencing of the spinal cord of a severe SMA mouse model, and identified ten cell types as well as their differentially expressed genes. Using CellChat, we found that cellular communication between different cell types in the spinal cord of SMA mice was significantly reduced. A dimensionality reduction analysis revealed 29 cell subtypes and their differentially expressed gene. A subpopulation of vascular fibroblasts showed the most significant change in the SMA spinal cord at the single-cell level. This subpopulation was drastically reduced, possibly causing vascular defects and resulting in widespread protein synthesis and energy metabolism reductions in SMA mice. This study reveals for the first time a single-cell atlas of the spinal cord of mice with severe SMA, and sheds new light on the pathogenesis of SMA.

Laryngeal cancer is one of the most common fatal cancers in head and neck carcinomas, but its mechanism is still unclear. The zonula occludens-1 (ZO-1) is closely related to the genesis and development of a variety of respiratory tract and gastrointestinal tumors but the expression of ZO-1 in laryngeal squamous cell carcinoma (LSCC) and its correlation with clinicopathologic features still remain undetermined. The aim to this study is to identify the clinical significance of ZO-1 in laryngeal cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry with tissue microarrays were used to characterize the expression of the ZO-1 mRNA and protein in LSCC. The statistical analysis was carried out by combining the follow-up data and clinicopathologic features. Both the ZO-1 mRNA and protein expressions in LSCC are lower than their expressions in corresponding peritumoral tissue (P<0.05); the ZO-1 expression is related to tumor differentiation (P=0.009), clinicopathological stages (P=0.025) and lymphatic metastasis (P=0.013). As shown in the Cox regression analyses, the ZO-1 expression (P=0.035), tumor location (P=0.030), lymphatic metastasis (P=0.002) and tumor differentiation (P=0.004) are independent prognostic factors. The ZO-1 can serve as an independent prognostic factor of LSCC and the high expression of ZO-1 is associated with good prognosis.