A study, published in the journal Cell, reveals that scientists have isolated amazing regenerative cells that have the potential to regrow an entire planarian. The study involved researchers at the Stowers Institute for Medical Research. They have captured the one cell that is capable of regenerating an entire organism.
It has been over a century that scientists have witnessed the effects of this cellular wonder. It enables creatures like flatworms to regrow their body parts. Flatworms like planaria accomplish death-defying acts like regrowing a severed head.
The researchers were lacking the tools required to target and track this cell, so they could watch it in action and discover its secrets. However, this research pioneers a technique that combines genomics, single-cell analysis, flow cytometry, and imaging. Thus, it reports the isolation of a regenerative cell i.e. a subtype of the long-studied adult pluripotent stem cell.
The findings of the study were published on June 14, 2018. They will possibly drive biological studies on highly regenerative organisms like planaria. Moreover, they inform regenerative medicine attempts for other organisms like humans, possessing less capacity for regeneration.
According to the researchers, this is the very first time that an adult pluripotent stem cell has been isolated prospectively. The study basically clarifies that there truly is a cellular entity that restores the regenerative capacities to animals that have lost it. Most importantly, the study is significant because it reports the purification and detailed study of the respective cell.
Every multicellular organism originates from a single cell. This cell undergoes a continuous cycle of cell division, giving rise to a set of cells with the same twisted strands of DNA. This cell is termed pluripotent which means that it can give rise to all possible cell types in the body. These starter cells are also known as embryonic stem cells. Each one of them has a different fate. They differentiate into skin cells, heart cells, muscle cells, or another cell type.
Neoblasts are responsible for regeneration in flatworms
Humans are known to have no pluripotent stem cells after birth. On the other hand, planaria have adult pluripotent stem cells or neoblasts that stick around into adulthood. Scientists believe these neoblasts are responsible for the process of regeneration.
Neoblasts have been the subject of scientific inquiry since the late 1800s. However, it was only in the last couple of decades that scientists have been able to differentiate this powerful cell population. Using functional assays and molecular techniques, the scientists have shown that neoblasts are a homogenous cell population. They are actually a conglomeration of different subtypes, with diverse properties and different patterns of gene expression.
According to the research team, they might have to transplant over a hundred individual cells into as many worms to find the one pluripotent and regenerative cellular entity. The main aim behind this extensive research was just to find the one cell that fits the functional definition of a true neoblast. Similarly, the molecular definition of neoblasts demand identification of the genes expressing them. So for that purpose, the scientists had to destroy the cell for processing. However, there was no way to do that and keep the cell alive to track it during regeneration.
The research team began to search for a discerning characteristic that could spot this elusive cell ahead of time. One feature that had long been used to differentiate neoblasts from other cells is a stem cell marker known as piwi-1. Thus the scientists decided to start here.
What does the study say?
First of all, the cells, expressing piwi-1, were separated from those that did not express it. Then the cells, expressing the respective marker, were further divided into two groups.
- The cells expressing high levels of piwi-1 or the piwi-high group
- The cells expressing low levels of piwi-1 or the piwi-low group
The results of the study showed that the cells belonging with the first group fit the molecular definition of neoblasts. So the rest of the cellular entities were discarded.
This kind of real-time, concurrent quantitative analysis of gene expression and protein levels had never been done before in planaria. The amazing scientific support facilities at Stowers Institute made this study possible. These conveniences included molecular biology, flow cytometry, bioinformatics, and imaging groups.
Furthermore, the researchers selected 8,000 cells from the piwi-high group for analyzing their patterns of gene expression. To their surprise, the cells consisted of 12 different subgroups. The researchers excluded any subgroups with genetic signatures. Note, these signatures indicated that the cells were destined for a particular outcome, like muscle or skin. This elimination technique left the researchers with two subgroups that could still be pluripotent. They were named as
It was found that the cells in subgroup Nb2 expressed a gene, coding for a member of the tetraspanin protein family. Tetraspanin is a group of prehistoric and poorly understood surface proteins. The researchers prepared an antibody that could handle this protein. The antibody intended pulling the cells that carried it out of a mixture of other suspected neoblasts.
The researchers then transplanted the single purified cell into a planarian. Note, the animal was subjected to lethal levels of radiation before the transplantation of the cells. The researchers noted that these cells repopulated and rescued the irradiated animals. Moreover, these cells were found to be 14 times more consistent than the cells purified by older methods.
The marker, discovered by the scientists, is expressed not only in planaria but also in humans. This suggests that there are some conserved yet undiscovered mechanisms of regeneration in humans as well. Experts believe that this concept is applicable to any organism that has ever relied on stem cells.
This study was funded by Stowers Institute for Medical Research in collaboration with the Howard Hughes Medical Institute, and the National Institute of General Medical Sciences of the National Institutes of Health.
Regeneration is the potential of regrowing the lost body parts. It is widely observed in invertebrates. Some plants also possess this characteristic. Freshwater flatworm called planaria is a favorite of scientists, studying regeneration in research organisms. It has been over a century that neoblasts were traced for their regenerative powers in planaria. However, due to the lack of necessary tools and techniques, it was difficult to target the individual cells truly capable of regeneration.
This study is a milestone because it identifies a surface molecule called TSPAN-1 that can be used to purify regenerative neoblasts from similar cell types. The results of the study have significant implications in advancing the study of stem cell biology and regenerative medicine. Moreover, scientists hope that they might unlock this property in humans as well.