Scientists from the Stowers Institute for Medical Research in the US found the one adult stem cell capable of completely regenerating an entire organism. The study, published June 14, 2018 in the journal Cell, was conducted on planarians known for their amazing ability to regenerate.
For more than a hundred years it has been known that planarians, which belonging to the family of flatworms, can show real miracles of recovery. For example, if they are cut into many parts, each piece will regrow into a full-fledged animal. Until now, the lack of a technical base has not allowed scientists to discover the type of cells responsible for this process.
Each multicellular organism is built from a single cell, which divides into two identical cells, then four, and so on. Each of these daughter cells contains the same DNA strands and is considered pluripotent, meaning it can give rise to all possible cell types in the body.
However, over time, as they grow older, stem cells lose this property and become more specialized. In humans, no known pluripotent stem cells remain after birth. In planarians, they persist after growing up and are called adult pluripotent stem cells or neoblasts. Scientists believe these neoblasts hold the secret to regeneration of planarians. But they’ve unsuccessful to figure out exactly which type of neoblast works this magic.
“This is the first time that an adult pluripotent stem cell has been isolated prospectively”, – says Alejandro Sánchez Alvarado, Ph.D., an investigator at the Stowers Institute and senior author of the study. “Our finding essentially says that this is no longer an abstraction, that there truly is a cellular entity that can restore regenerative capacities to animals that have lost it and that such entity can now be purified alive and studied in detail.”
Scientists led by Sánchez Alvarado used new approach for isolating single cells and characterizing their gene activity, combining genomics, single cell analysis, flow cytometry and visualization, which helped identify 12 conceivable candidate cell types for a “master regenerative” cell. Among them was one type of cell that carried on the surface an unusual protein, tetraspanin, which takes part in the spread of cancer cells in humans throughout the body.
By marking the tetraspanin of the worm with a fluorescent marker, scientists were able to isolate this type of cells, which has received the name neoblast subtype No. 2 (Nb2), for further research. Monitoring of the regeneration of the planarian cut showed a significant increase in the number of these cells to cure a wound to the incision site.
In another experiment, a single injected neoblast No. 2 could multiply and differentiate to save the planarians who received a lethal dose of radiation.
Nb2 cells are a special type of stem cells. In other organisms, only at the earliest stages of embryo development, cells (known as totipotent cells) are capable of forming all body tissues. At later stages of human and animal life, stem cells can only differentiate into a limited type of cells.
Sánchez Alvarado explains that: “somehow planaria have retained cells”, which can turn into any others type they want.
The team of scientists found that Nb2 cells are always present throughout the planaria body. They increase gene activity to make tetraspanin only in injured animals. This protein may play a key role: when the scientists transplanted neoblasts that didn’t make tetraspanin in the dying planarians, the worms did not recover.
It is unclear why this protein is so important, but apparently he is involved in intercellular communication. The fact that tetraspanin plays a role in the spread of cancer cells means that it also helps stem cells get to the injured parts of the planaria for healing.
With the help of antibodies that can tag and isolate Nb2 cells, scientists can now look in more detail at how the tetraspanin works and the triggering of its production mechanism in these cells.
“We have enriched for a pluripotent stem cell population, which opens the door to a number of experiments that were not possible before”, – says Sánchez Alvarado. “The fact that the marker we discovered is expressed not only in planarians but also in humans suggests that there are some conserved mechanisms that we can exploit. I expect those first principles will be broadly applicable to any organism that ever relied on stem cells to become what they are today.”