First created a “road map” for the development of human skeletal muscles

US, WASHINGTON (ORDO NEWS) — Scientists from the University of California at Los Angeles have created the first roadmap for the development of human skeletal muscle, including the formation of muscle stem cells. Thanks to new data, in the future it is possible to develop more advanced methods for creating muscle cells from stem cells, which is important for the treatment of some serious diseases. An article about this is published in the journal Cell Stem Cell .

The authors identified various types of cells present in skeletal muscle tissue, from early embryonic development to adulthood. By focusing on muscle progenitor muscle cells, which contribute to muscle formation before birth, and muscle stem cells, which are responsible for muscle formation after birth, as well as their regeneration after injuries throughout life, the group was able to map on and off genes as the cells mature. .

The new roadmap is important for researchers who want to develop muscle stem cells in the laboratory: they are needed in regenerative cell therapy to treat destructive muscle diseases such as muscular dystrophy and sarcopenia, as well as age-related loss of muscle mass and strength. Such conditions are caused by malfunctioning of muscle stem cells, and the map, according to April Pyle, senior author of the article, identifies the exact gene network.

Scientists can already generate skeletal muscle cells from human pluripotent stem cells, which are capable of self-renewal and transformation into any other type. However, so far they have not had the opportunity to determine exactly where disruptions in the development of these cells occur.

“We knew that the muscle cells we made in the laboratory were not as functional as the fully mature muscle stem cells found in humans,” explains Haibin Xi, the first author of the new article. “So we decided to create this map as a reference that our laboratory and others can use to compare the genetic signatures of the cells we create with the signatures of real human skeletal muscle tissue.”

The authors collected specific data on two different groups of skeletal muscle cells: taken from the human body from the fifth week of embryonic development to middle age and taken from human pluripotent stem cells that the researchers created in the laboratories. They then compared the genetic characteristics of cells from both sources.

Specialists performed high-performance dropwise RNA sequencing: this technology allows the identification of gene networks present in one cell, and can process data on thousands of cells simultaneously. With its help, the group determined the genetic traits of various types of cells from human tissues and pluripotent stem cells.

Using specially designed computational algorithms, the authors were able to identify specific gene networks associated with each stage of development. This allowed us to compare the genetic traits found in pluripotent muscle cells obtained from stem cells with their corresponding locations on the map of human muscle development.

It turned out that those muscle cells that were obtained from pluripotent stem cells, regardless of the method of their production, resembled muscle progenitor cells in an early state of development and did not align with adult muscle stem cells over time.

In addition to determining the true maturity of laboratory-produced cells, this analysis provided detailed information about other types of cells present in skeletal muscle tissue during development and populations derived from human pluripotent stem cells. These cells can play a significant role in muscle cell maturation and are critical to improving in vitro muscle stem cell generation and support.

“We found that some in vitro muscle cell generation methods also produce unique cell types that probably support muscle cells,” says Pyle. “So now our questions are: what do these cells do?” Could they be the key to producing and supporting in vitro mature and functional muscle stem cells? ”

Moving forward, Pyle and her colleagues will focus on using this new resource to develop better methods for producing muscle stem cells from human pluripotent stem cells in the laboratory. She hopes that by focusing on gene expression networks associated with stem cells and the supporting cell types identified by them, powerful muscle stem cells can be produced that will be useful for future regenerative therapy.

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