Israeli breakthrough: Cells expressing tendon markers fuse into muscles

Israeli breakthrough: Cells expressing tendon markers fuse into muscles

The foot bone’s connected to the leg bone; the leg bone’s connected to the knee bone; the knee bone’s connected to the thigh bone; the thigh bone’s connected to the hip bone; the hip bone’s connected to the backbone; the backbone’s connected to the neck bone. We have heard this from the 1929 Skeleton Dance produced and directed by Walt Disney  (so it must be true..).

But what actually connects these bones to the muscles? It’s the tendons – dense connective tissues or sinews that are capable of withstanding tension and transmit the mechanical forces of muscle contraction to the skeletal system.  The tendons’ mechanical properties are crucial for humans and other vertebrates to bear varying pressures and perform essential movements. 

When the development of muscle tendon junctions (MTJs) is damaged, it ciykd result in various kinds of muscle diseases. Therefore, understanding the molecular mechanism underlying MTJ development is very important.

Researchers at the Rappaport Faculty of Medicine at the Technion – Israel Institute of Technology in Haifa – in a scientific breakthrough –

discovered that muscle fibers are of hybrid origins and their tips have a fibroblastic, tendon-like property that arises from fibroblasts’ fusion. The researchers’ findings highlight a mechanism that enables a smooth transition from muscle fiber characteristics towards tendon features that is essential for forming robust MTJs. 

Prof. Peleg Hasson (right) and doctoral student Wesal Yaseen Badarneh (Doron Shaham-Marcus, Technion Dropbox)

The research was recently published in Nature Communications under the title “Fibroblast fusion to the muscle fiber regulates myotendinous junction formation.” 

Using innovative techniques for analyzing single cells (scRNAseq), Prof. Peleg Hasson and doctoral student Wesal Yaseen Badarneh reexamined the classical view of distinct identities for the tissues composing the musculoskeletal system. The research was carried out in collaboration with researchers from the University of Cincinnati College of Medicine and the Cincinnati Children’s Hospital Medical Center. They identified a novel cluster of cells, which they termed dual identity cells. 

These dual identity cells are fibroblast-derived, yet they express myogenic transcriptional programs and fuse into the tips of the developing muscle fibers along the muscle tendon junctions, facilitating the introduction of fibroblast-specific transcripts into the elongating myofibers.

Although vertebrate muscles and tendons are derived from distinct embryonic origins, they must interact to enable muscle contraction and body movements. Scientists have not really understood how these two distinct tissues, each with its own biophysical and biochemical properties, form robust junctions that are able to withstand contraction forces – even though it is critical for muscle functioning in transmitting the force generated by the muscle to the tendons and skeletal elements. 

Hasson and his team identified fibroblasts that have switched on a myogenic program facilitating a seamless transition from a muscle fiber characteristic into a tendon-like structure. Their findings suggest that dual characteristics of junctional cells could be a common mechanism for generating stable interactions between tissues throughout the musculoskeletal system.