Search

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Background: Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized by early onset muscle weakness leading to severe and irreversible disability. Muscle degeneration involves a complex interplay between multiple cell lineages spatially located within areas of damage, termed the degenerative niche, including inflammatory cells, satellite cells (SCs) and fibro-adipogenic precursor cells (FAPs). FAPs are mesenchymal stem cell which have a pivotal role in muscle homeostasis as they can either promote muscle regeneration or contribute to muscle degeneration by expanding fibrotic and fatty tissue. Although it has been described that FAPs could have a different behavior in DMD patients than in healthy controls, the molecular pathways regulating their function as well as their gene expression profile are unknown. Methods: We used single-cell RNA sequencing (scRNAseq) with 10X Genomics and Illumina technology to elucidate the differences in the transcriptional profile of isolated FAPs from healthy and DMD patients. Results: Gene signatures in FAPs from both groups revealed transcriptional differences. Seurat analysis categorized cell clusters as proliferative FAPs, regulatory FAPs, inflammatory FAPs, and myofibroblasts. Differentially expressed genes (DEGs) between healthy and DMD FAPs included upregulated genes CHI3L1, EFEMP1, MFAP5, and TGFBR2 in DMD. Functional analysis highlighted distinctions in system development, wound healing, and cytoskeletal organization in control FAPs, while extracellular organization, degradation, and collagen degradation were upregulated in DMD FAPs. Validation of DEGs in additional samples (n = 9) using qPCR reinforced the specific impact of pathological settings on FAP heterogeneity, reflecting their distinct contribution to fibro or fatty degeneration in vivo. Conclusion: Using the single-cell RNA seq from human samples provide new opportunities to study cellular coordination to further understand the regulation of muscle homeostasis and degeneration that occurs in muscular dystrophies. [ABSTRACT FROM AUTHOR]

We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at (https://www.covid19cellatlas.org/). An analysis of single-cell transcriptomics datasets from different tissues shows that ACE2 and TMPRSS2 are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of ACE2 is associated with genes involved in innate immunity., Author(s): Waradon Sungnak [sup.1] , Ni Huang [sup.1] , Christophe Bécavin [sup.2] , Marijn Berg [sup.3] [sup.4] , Rachel Queen [sup.5] , Monika Litvinukova [sup.1] [sup.6] , Carlos Talavera-López [sup.1] [...]

This study examined the outcomes of 409 students with mental retardation or multiple disabilities from 177 school districts in a Great Lakes state. These students with intellectual disabilities were interviewed at exit and 1 year following graduation. The authors developed and tested three regression models--two to predict full-time employment and one to predict college enrollment after graduation. Although inclusion was a significant predictor of postsecondary education, career and technical education and work study programs did not reach significance as predictors of postschool employment. For these students, gender and minority issues contributed to most of the variance. These findings point to the need for more holistic career and technical education and work study models for these students. (Contains 7 tables.)

This longitudinal transition study was conducted in collaboration with teachers who interviewed students who graduated from 177 school districts in a Great Lakes state. Special education students were interviewed at exit and 1 year following graduation using a survey based on the National Longitudinal Transition Study. The data were analyzed using logistic regression models that controlled for gender, minority status, and level of disability. The authors developed and tested three regression models: two to predict full-time employment and one to predict college enrollment. Students who graduated from career and technical education and work study programs were more likely to enter full-time employment after graduation, but this relationship was influenced by gender, minority status, and disability. Students who participated in mainstream academics were much more likely to be enrolled in full-time college after graduation, but this relationship was influenced by level of disability. (Contains 6 tables and 2 figures.)

The purpose of this study was to examine disproportionality in transition services for students with disabilities. The authors predicted that students' transition services and secondary programs would be driven not only by their postschool goals, but also by their gender, ethnicity, disability, and school setting. To test this hypothesis, the researchers examined school records and interviews of more than 4,500 students in a northeastern state who graduated or aged out of special education in the years 2005-2008. The authors found that secondary programs and transition services varied significantly for students from differing school settings and differing gender, ethnicity, and disability groups and that this often resulted in poor alignment between students' goals and their secondary curricula and transition services. The authors propose that these findings indicated the need for earlier transition planning and better connections between middle and high schools. (Contains 3 tables.)

The authors describe the implementation and impact of a graduate-level transition personnel preparation program for transition specialists. This program was based on the Council for Exceptional Children (CEC) standards for transition specialists. Over 200 special educators were prepared in a 2-year part-time graduate program where interdisciplinary, practice-based preparation was provided. Participants completed five courses and one practicum designed to prepare them to meet the standards for transition specialists. Competency ratings significantly improved after program completion. Focus group responses suggested that the program design had features that had major impact on the areas of policy, collaboration, and leadership. Collaboration and interdisciplinary activities emphasizing the roles of transition professionals were described throughout the article, showing how transition specialists, career/technical educators, and rehabilitation counselors are mutually supportive of youth with disabilities achieving postschool goals. The authors recommended further research on how this kind of preparation might be disseminated and replicated. [ABSTRACT FROM AUTHOR]