Researchers at the Stowers Institute for Medical Research have captured the one cell that is capable of regenerating an entire organism. For over a century, scientists have witnessed the effects of this cellular marvel, which enables creatures such as the planarian flatworm to perform death-defying feats like regrowing a severed head. But until recently, they lacked the tools necessary to target and track this cell, so they could watch it in action and discover its secrets.
“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 Howard Hughes Medical 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.”
Every multicellular organism is built from a single cell, which divides into two identical cells, then four, and so on. Each of these cells contains the exact same twisted strands of DNA, and is considered pluripotent — meaning it can give rise to all possible cell types in the body. But somewhere along the way, those starter cells — known as embryonic stem cells — resign themselves to a different fate and become skin cells, heart cells, muscle cells, or another cell type. In humans, no known pluripotent stem cells remain after birth. In planarians, they stick around into adulthood, where they become known as adult pluripotent stem cells or neoblasts. Scientists believe these neoblasts hold the secret to regeneration.
Finding it wasn’t easy:
“We might have to transplant over a hundred individual cells into as many worms to find one that is truly pluripotent and can regenerate the organism,” says Sánchez Alvarado. “That’s a lot of work, just to find the one cell that fits the functional definition of a true neoblast. And if we want to define it molecularly by identifying the genes that cell is expressing, we have to destroy the cell for processing. There was no way to do that and keep the cell alive to track it during regeneration.”
“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. And that essentially is everybody.” Paper. (paywall) – An Zeng, Hua Li, Longhua Guo, Xin Gao, Sean McKinney, Yongfu Wang, Zulin Yu, Jungeun Park, Craig Semerad, Eric Ross, Li-Chun Cheng, Erin Davies, Kai Lei, Wei Wang, Anoja Perera, Kate Hall, Allison Peak, Andrew Box, Alejandro Sánchez Alvarado. Prospectively Isolated Tetraspanin Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration. Cell, 2018; 173 (7): 1593 DOI: 10.1016/j.cell.2018.05.006 More.
From Elizabeth Pennisi at Science:
He and his colleagues discovered that Nb2 cells are always present throughout the planaria body. But they increase gene activity to make tetraspanin only in wounded individuals. And the protein seems key: When the researchers put neoblasts that didn’t make tetraspanin in dying planaria, the planaria did not recover.
It’s not yet clear why this protein is so important, but it seems to be involved in cell-to-cell communication. Its role in spreading cancer cells suggests it may also help cells get to parts of the planaria that need fixing. More.
Accounts of the evolution of such systems will be interesting. It’s probably still not as simple as hoped.
See also: There are now many variants of the universal genetic code
We hesitated to bring you the Frankenflatworm … “Call them Franken flatworms. Scientists have created worms with the heads and brains of other species just by manipulating cell communication.”
Pond hydra can modify its own genetic program. But then this is the same life form that can reassemble from a small piece, and lose all its neurons but live.