Abstract
Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. WBR cannot proceed when proliferating IA6+ cells are ablated with Mitomycin C, and injection of a single IA6+ Candidate stem cell can rescue WBR after ablation. Lineage tracing using EdU-labeling demonstrates that donor-derived IA6+ Candidate stem cells directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of IA6+ Candidate stem cells, indicating that these two pathways regulate their activation. In conclusion, we show that IA6+ Candidate stem cells are responsible for whole body regeneration and give rise to regenerating tissues.
Highlights
Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels
To assess whether Integrin-alpha-6 enriches for cells expressing stem cell-associated genes in B. diegensis, we used an antibody against the extracellular part of human Integrin-alpha-6 (IA6)
An alignment of human and B. diegensis integrin alpha 6 protein sequences shows that both proteins share significant overlap (=50% positive amino acid alignment)
Summary
Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Some invertebrate species within the Platyhelminthes, Cnidaria, and Echinodermata, can regenerate whole bodies from small fragments of tissue, while some vertebrates such as amphibians and fish can regenerate ablated limbs and distal structures of some organs Groups such as insects, birds, and mammals have nearly lost the ability to regenerate[1,2,3]. A group of invertebrate chordate species; colonial ascidians of the genus Botrylloides, have been shown to regenerate whole bodies, including all tissues and organs, from small fragments of the vasculature. This process is called Whole Body Regeneration (WBR)[5,6,7,8,9,10]. WBR can be induced in fragments as small as 5 ampullae, and is not dependent on the stage of asexual reproduction of the colony[5,7]
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