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Who’s the Boss?

Posted on April 25, 2019

Researchers from McMaster University have found a subset of stem cells in the human body that signal how cells around it will develop. The subset of stem cells, thought to be unique in the body, have been dubbed “kingpin” cells, or human pluripotent founder cells.

Their discovery, along with the process used to identify the cells, could mean the potential for new research into understanding how cancerous tumors develop and grow.

The researchers also hope for more insight into how human stem cells “decide” on what tissue they are going to become.

“Stem cells are the foundations of the body; they are the basis of every organ and tissue we have,” said Dr. Joel Singer, a New York personal cell physician who was not involved in the study.

Stem cells are also crucial for repairing the body after injury and illness.

“Stem cells lie dormant in the body until called up for repair. When signaled, they go to work, differentiating themselves into the type of tissue needed for the injured area,” Singer said.

Pluripotent stem cells (PSCs) are some of the most potent stem cells in the body, with the ability to develop into a range of tissues. Other stem cells, such as mesenchymal stem cells found in fat tissue, can develop into connective tissues such as muscle, cartilage, tendons, bones and blood vessels.

The kingpin cells are suspected to be even more powerful than PSCs.

“There are other types of stem cells throughout the body, some of which can regenerate quickly, and some that don’t – like neural stem cells,” Singer said.

These kingpin stem cells were not known to exist before the study. They appear to manage the stem cell ecosystem and send signals to other cells.

The researchers found that these specialized cells have very different genes than other stem cells. They also follow a different set of rules and respond to different signals compared to other cells.

The research project took more than six years, with researchers diving deep into the cellular level to examine cells they previously overlooked. The cells, located on the edges of pluripotent stem cell colonies, were observed from early stages of development.

Using a single-cell RNA-sequencing gene expression analysis, the researchers found the cells and were able to note their differences compared to other cells around them.

The founder cells were also compared to stem cells taken from mice, but researchers did not find similarities. Interestingly, the researchers did find the same subset of kingpin cells in primate stem cells.

These findings surprised researchers, who thought that the existence of the cells would be universal. It turns out, they are only found in primates.

The McMaster researchers believe that this fundamental difference could be why mice respond differently during stem cell therapy than humans do.

The team is now using their findings about the founder cells and the usefulness of single-cell RNA sequencing to analyze the cells to find answers about human cancer.

Primarily, they are hoping to answer questions about why individual cells become cancerous and what are the fundamental differences between cancer cells.

They are also interested in finding out if these kingpin cells are found in cancerous tumors in humans.

“Identifying where and what these cells could do may mean new preventatives and interventions for cancer,” said Singer.

The study was initially funded by the Natural Sciences and Engineering Research Council of Canada as well as the Canadian Institutes of Health Research.

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