These used a technique that combines genomics, single-cell analysis, flow cytometry and imaging, scientists have isolated this amazing regenerative cell – a subtype of the long-studied adult pluripotent stem cell – before it performs its remarkable act. This will propel biological studies on highly regenerative organisms like planarians and also inform regenerative medicine efforts for other organisms like humans that have less regenerative capacity.
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.
Though neoblasts have been the subject of scientific inquiry since the late 1800’s, only in the last couple of decades have scientists been able to characterize this powerful cell population using functional assays and molecular techniques. Their efforts showed that this seemingly homogenous cell population was actually a conglomeration of different subtypes, with different properties and different patterns of gene expression.
Highlights -Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration
•piwi-1 RNA and protein expression defined spectrum of functional neoblast states
•scRNA-seq defined 12 neoblast sub-types; sub-type Nb2 contains pluripotent stem cells
•Transplantation of single TSPAN-1+ Nb2 cells rescued lethally irradiated animals
•Nb2 transcriptome differs during homeostasis, sublethal irradiation, and regeneration
Summary -Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration
Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Large-scale scRNA-seq of sorted neoblasts unveiled a novel subtype of neoblast (Nb2) characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 (tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. The first prospective isolation of an adult PSC bridges a conceptual dichotomy between functionally and molecularly defined neoblasts, shedding light on mechanisms governing in vivo pluripotency and a source of regeneration in animals.
AgeX working to revive embryonic regeneration to enable a body to fully regenerate and repair aging damage
AgeX is leading off with cell-based regenerative therapeutics for significant unmet needs in age-related disease such as Type II diabetes (using its manufactured brown adipocyte product (AGEX-BAT1)), and ischemic disease (using its young vascular progenitor cell product (AGEX-VASC1)). In addition, it will also be advancing products based on an entirely new technology platform aimed at the central molecular processes of aging itself designated “induced Tissue Regeneration (iTR)” AgeX scientists believe that the combination of telomerase therapy and iTR may unlock the potential of immortal tissue regeneration in humans. Model organisms that display immortal tissue regeneration show no evidence of aging.
The combination of pluripotent stem cell and iTR technology may provide AgeX with a highly differentiated and valuable platform to address large markets associated with chronic degenerative age-related disease.
Induced Tissue Regeneration
Some naturally-occurring animals such as the Mexican salamander can profoundly regenerate damaged tissues. Humans also have this potential, but only in the first weeks of development. Using advanced molecular and artificial intelligence technologies, we have identified pathways we believe may provide means of unlocking this profound biology in human medicine. The pathways suggest that they may also be integral to the biology of aging and cancer as well. Patents relating to this emerging technology called induced Tissue Regeneration (iTR), have been filed and animal studies are currently underway. iTR was the subject of a recent conference presentation from AgeX CEO Dr. Michael West.