Category Archives: כתבות אמצע

Researchers at the Rappaport Faculty of Medicine at the Technion – Israel Institute of Technology have made a breakthrough discovery 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 muscle tendon junctions (MTJs). The research was recently published in Nature Communications.

Using innovative techniques for analyzing single cells (scRNAseq), Professor Peleg Hasson and doctoral student Wesal Yaseen Badarneh reexamined the classical view of distinct identities for the tissues composing the musculoskeletal system. They identified a novel cluster of cells, which they termed dual identity cells. These dual identity cells are fibroblast-derived, yet 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.

Tendons are the connective tissues that connect between the muscles and bones. Consequently, the tendons’ mechanical properties are crucial in order for humans and other vertebrates to bear varying pressures and perform essential movements. When the development of MTJs is damaged, it may result in clinical phenomena including multiple types of muscle diseases. Therefore, understanding the molecular mechanism underlying MTJ development is very important.

Although vertebrate muscles and tendons are derived from distinct embryonic origins, they must interact in order to enable muscle contraction and body movements. It is still not understood how these two distinct tissues, each with its own biophysical and biochemical properties, form robust junctions that are able to withstand contraction forces. Prof. 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.

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. It was supported by the Israel Science Foundation, the Rappaport Family Institute at Technion, Pew Charitable Trusts, and the National Institutes of Health (NIH).

Click here for the paper in Nature Communications

A study conducted in the Technion Faculty of Biology sheds light on the structure and dynamics of chromatosomes. Published in the journal Molecular Cell, the study was conducted by Dr. Sergei Rudnizky under the supervision of Professors Ariel Kaplan and Philippa Melamed.

Each one of the cells in our body contains DNA, which provides the instructions required for our development and function. Astoundingly, a total of two meters of DNA is packaged in each cell’s nucleus, just tens of microns in size, a feat accomplished by packaging the DNA into a compact structure called chromatin. The basic level of chromatin organization is provided by wrapping the DNA around proteins called histones in a spool-like structure that resembles “beads on a string.” Then, more complex structures called chromatosomes are formed with the help of a special histone, known as a “linker histone,” which connects the “strings.”

Packaging of the genome is essential in order for it to fit into the cell, but it also reduces the accessibility to the cellular machines that read the DNA and transcribe the genes. Thus, the distinct packaging at a particular gene will have a huge impact on its expression, in ways that are only beginning to be unraveled. In particular, linker histones are known to play a key role in this organization of the genome, and their malfunctions can lead to serious diseases including cancer and autism, but the most basic questions of how they bind DNA are still unanswered.

The lack of understanding of these crucial processes stems from the dynamic nature of linker histones, which makes it challenging to investigate them using conventional methods based on sampling a huge number of molecules simultaneously. In order to overcome this problem, Prof. Kaplan’s lab developed a unique method based on “optical tweezers,” an approach that allows researchers to capture individual chromatin molecules and exert forces on them with the help of a focused laser beam. In these experiments, one strand of DNA is slowly detached from its complementary strand in a manner similar to a zipper being unzipped, through the entire structure of a chromatosome. The principle of the measurement is simple: at points where a histone makes contact with the DNA, even in the weakest way, the zipper gets stuck, and more force needs to be applied to overcome the histone-DNA contact and advance into the structure.

Using this approach, Dr. Rudnizky and his coworkers discovered that contacts between histones and DNA are far more extensive than previously known, and that chromatosomes are, in fact, much larger than previously thought. Moreover, they found a surprising flexibility in the structure of linker histones, as two different chromatosome shapes exist: one symmetric and compact, and the second asymmetric and more relaxed. Remarkably, transition between these shapes in an individual molecule can be externally controlled by the transcription machinery itself. This suggests that the cell utilizes the transition between stable and unstable forms of a chromatosome to regulate access to the DNA in a controlled manner. Given the key role played by chromatosomes in maintaining proper expression of our genome, these findings add an important layer to our understanding of the role of chromatin architecture in health and disease.

For the article in Molecular Cell, click here.