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Single-cell transcriptomic analysis identifies extensive heterogeneity in the cellular composition of mouse Achilles tendons.

ABSTRACT: Tendon is a dense connective tissue that stores and transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, yet little is known about the diversity of cell types that populate tendon. To address this, we determined the heterogeneity of cell populations within mouse Achilles tendons using single-cell RNA sequencing. In assembling a transcriptomic atlas of Achilles tendons, we identified 11 distinct types of cells, including three previously undescribed populations of tendon fibroblasts. Prior studies have indicated that pericytes, which are found in the vasculature of tendons, could serve as a potential source of progenitor cells for adult tendon fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are likely to be at least one of the progenitor cell populations for the fibroblasts that compose adult tendons. We also modeled cell-cell interactions and identified previously undescribed ligand-receptor signaling interactions involved in tendon homeostasis. Our novel and interactive tendon atlas highlights previously underappreciated heterogeneity between and within tendon cell populations. The atlas also serves as a resource to further the understanding of tendon extracellular matrix assembly and maintenance and in the design of therapies for tendinopathies.

SUBMITTER: De Micheli AJ

PROVIDER: S-EPMC7701267 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesUltrasound often corroborates clinical diagnosis of Achilles tendinopathy (AT). Traditional measures assess macromorphological features or use qualitative grading scales, primarily focused within the free tendon. Shear wave imaging can non-invasively quantify tendon elasticity, yet it is unknown if proximal structures are affected by tendon pathology. The purpose of the study was to determine the characteristics of both traditional sonographic measures and regional shear wave speed (SWS) between limbs in patients with AT.MethodsTwenty patients with chronic AT were recruited. Traditional sonographic measures of tendon structure were measured. Regional SWS was collected in a resting ankle position along the entire length of the tendon bilaterally. SWS measures were extracted and interpolated across evenly distributed points corresponding to the free tendon (FT), soleus aponeurosis (SA), and gastrocnemius aponeurosis (GA). Comparisons were made between limbs in both traditional sonographic measures and regional SWS.ResultsSymptomatic tendons were thicker (10.2 (1.9) vs. 6.8 (1.8) mm; p < 0.001) and had more hyperemia (p = 0.001) and hypoechogenicity (p = 0.002) than the contralateral tendon. Regional SWS in the FT was lower in the symptomatic limb compared to the contralateral limb (11.53 [10.99, 12.07] vs. 10.97 [10.43, 11.51]; p = 0.03). No differences between limbs were found for the SA (p = 0.13) or GA (p = 0.99).ConclusionsLower SWS was only observed in the FT in AT patients, indicating that alterations in tendon elasticity associated with AT were localized to the FT and did not involve the proximal passive tendon structures.Key points• Baseline characteristics of a pilot sample of 20 subjects suffering from chronic Achilles tendinopathy showed differences in conventional sonographic measures of tendon thickness, qualitatively assessed hypoechogenicity, hyperemia, and quantitative measures of shear wave speed. • Regional shear wave speeds were lower in the free tendon but not in the proximal regions of the soleus or gastrocnemius aponeuroses in Achilles tendinopathy patients. • Using shear wave imaging to estimate tendon stiffness may prove beneficial for clinical validation studies to address important topics such as return to activity and the effectiveness of rehabilitation protocols.

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Single-cell transcriptomic analysis identifies extensive heterogeneity in the cellular composition of mouse Achilles tendons.

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