Single-nucleus transcriptional and chromatin accessibility analyses of maturing mouse Achilles tendon uncover the molecular landscape of tendon stem/progenitor cells

• DOI: 10.7554/elife.104768
• Publication Date: 2025-02-27T12:25:40Z
• Authors: Hiroki Tsutsumi; Tomoki Chiba; Yuta Fujii; Takahide Matsushima; Tsuyoshi Kimura; Akinori Kanai; Akio Kishida; Yutaka Suzuki; Hiroshi Asahara
• Keywords: Progenitor

Tendons and ligaments are crucial connective tissues linking bones muscles, yet achieving full functional recovery after injury remains challenging. We investigated the characteristics of tendon stem/progenitor cells (TSPCs) by focusing on declining repair capacity with growth. Using single-cell RNA sequencing Achilles from 2- 6-week-old mice, we identified Cd55 Cd248 as novel surface antigen markers for TSPCs. Combining single-nucleus ATAC analyses revealed that positive fractions in tissue TSPCs, this population decreasing at 1 weeks. also candidate upstream transcription factors regulating these fractions. Functional isolated CD55/CD248 demonstrated high clonogenic potential differentiation capacity, forming tendon-like vitro . This study establishes CD55 CD248 TSPC antigens, potentially advancing regenerative medicine contributing to development new treatment strategies ligament injuries.