The Lineage Differentiation and Dynamic Heterogeneity of Thymic Epithelial Cells During Thymus Organogenesis.

Although much progress has been made recently in revealing the heterogeneity of the thymic stromal components, the molecular programs of cell lineage divergency and temporal dynamics of thymic epithelial cell (TEC) development are largely elusive. Here, we constructed a single-cell transcriptional landscape of non-hematopoietic cells from mouse thymus spanning embryonic to adult stages, producing transcriptomes of 30,959 TECs. We resolved the transcriptional heterogeneity of developing TECs and highlighted the molecular nature of early TEC lineage determination and cortico-medullary thymic epithelial cell lineage divergency. We further characterized the differentiation dynamics of TECs by clarification of molecularly distinct cell states in the thymus developing trajectory. We also identified a population of Bpifa1+ Plet1+ mTECs that was preserved during thymus organogenesis and highly expressed tissue-resident adult stem cell markers. Finally, we highlighted the expression of Aire-dependent tissue-restricted antigens mainly in Aire+ Csn2+ mTECs and Spink5+ Dmkn+ mTECs in postnatal thymus. Overall, our data provided a comprehensive characterization of cell lineage differentiation, maturation, and temporal dynamics of thymic epithelial cells during thymus organogenesis.

Surgical or nonsurgical treatment for nontraumatic rotator cuff tears: Study protocol clinical trial.

BACKGROUND: The optimal treatment for symptomatic, nontraumatic rotator cuff tear is unknown. The primary aim of this randomized controlled trial is to compare functional improvement after surgical and conservative treatment of nontraumatic rotator cuff tears. METHODS: This is a single-centre, randomized clinical trial with a follow-up of 12 months. Patients older than 18 years with magnetic resonance imaging - confirmed nontraumatic rotator cuff tears that are suitable for either surgery or nonsurgery treatment is enrolled. The primary outcome is Constant score. Secondary outcome measures include visual analog scale (VAS) score, patient satisfaction, and American Shoulder and Elbow Surgeons (ASES) score. All scores are assessed by an independent observer who is blinded to the allocation of groups. RESULTS: The study will provide much needed data on surgical vs nonsurgical treatment for nontraumatic rotator cuff tears. Results of this study may help patients, clinicians, and policy makers assess the pivotal question on comparative effectiveness of surgery vs nonsurgical for rotator cuff tears. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5442).