Planaria flatworm (credit: Holger Brandl et al./Wikipedia)
In the June 14, 2018, issue of the journal Cell, researchers at Stowers Institute for Medical Research published a landmark study whose findings have important implications for advancing the study of stem cell biology and regenerative medicine, according to the researchers.*
Over a century ago, scientists traced regenerative powers in a flatworm known as planaria to a special population of planaria adult stem cells called neoblasts (a type of adult pluripotent stem cell — meaning a cell that can transform into any type of cell). Scientists believe these neoblasts hold the secret to regeneration. But until recently, scientists lacked the tools necessary to identify exactly which of the individual types of neoblasts were actually capable of regeneration.
However, with a special technique that combined genomics, single-cell analysis, and imaging, the scientists were able to identify 12 different subgroups of neoblasts. The problem was to find the specific neoblasts that were pluripotent (able to create any kind of cell, instead of becoming specific cells, like muscle or skin). By further analyzing the 12 neoblast markers (genetic signatures), they narrowed it down one specific subgroup, called Nb2.
Planarian flatworm adult stem cells known as neoblasts can be clustered based on their gene expression profiles (left panel). A neoblast subpopulation termed Nb2 expresses the cell membrane protein TSPAN-1 (center panel, a representative Nb2 cell with TSPAN-1 protein shown in green and DNA in blue). Nb2 neoblasts were found to be able to repopulate stem cell-depleted animals (right panel, representative animals at different time points after Nb2 single-cell transplants). (credit: Stowers Institute for Medical Research)
To see if the Nb2 type of neoblast was truly capable of regeneration, they irradiated a group of planaria and then inserted the Nb2 into the planaria. They found the Nb2 subgroup was in fact able to repopulate the planaria.
“We have enriched for a pluripotent stem cell population, which opens the door to a number of experiments that were not possible before,” says senior author Alejandro Sánchez Alvarado, Ph.D. “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.”
Ref.: Cell. Source: Stowers Institute for Medical Research
* The work was funded by the Stowers Institute for Medical Research, the Howard Hughes Medical Institute, and the National Institute of General Medical Sciences of the National Institutes of Health.