The invertebrate chordate Botrylloides leachii regenerates entire new bodies from small fragments of blood vessels in a process called whole body regeneration (WBR). During the early stages of WBR, proliferation occurs only in small, blood borne cells expressing integrin-alpha-6, pou3 and vasa. Proliferating blood cells can be ablated using Mitomycin C (MMC), and MMC treatment blocks regeneration. However, regeneration could be rescued by injection of blood borne cells from healthy individuals, and injection of a single Integrin-alpha-6 (IA6)-positive cell is capable of rescuing whole body regeneration. Following transplantation of EdU-labeled IA6+ cells into MMC treated recipients, EdU label is detected in regenerating tissues. Our data suggest that ia6+pou3+ cells are proliferating blood borne stem cells that are responsible for whole body regeneration, and we named these cells Primordial Blasts. Primordial Blasts express notch and frizzled receptors, and inhibitors of either Notch or canonical Wnt signaling block regeneration and proliferation of Primordial Blasts.