Figure 1

Origin of blastemal progenitor cells in vertebrate regeneration. Lineage restriction during vertebrate regeneration has become the accepted norm, but multiple mechanisms might function to generate the blastema cells. (a) Non-muscle tissues contain different lineage-restricted (for example, epidermis, nervous system or bone) stem-like cells that produce progenitor cells that have distinct fates. In addition, natural dedifferentiation of a postmitotic cell can generate a proliferation-competent cell within the same lineage, which in turn produces a pool of progenitor cells. (b) Skeletal muscle is composed of multinucleated fibers and satellite cells (muscle stem cells). The satellite cells self-renew and produce new differentiated muscle fibers. However, multinucleated muscle fibers can dedifferentiate and fragment to generate a pool of progenitor cells. The dedifferentiation process is accompanied by the disassembly of the sarcomeric contractile apparatus, giving rise to proliferation-competent monocytes, which are similar to satellite cells. These muscle progenitor cells divide and finally differentiate into new muscle. (c) Regeneration is accompanied by dramatic reorganization of the tissue extracellular matrix (ECM) environment at the wound site. A regeneration-specific matrix temporarily replaces the normal ECM and differentially directs cellular behaviors, including proliferation, myofiber fragmentation and myoblast fusion. An intriguing hypothesis would be that the regeneration-specific matrix also has a role in balancing dedifferentiation with stem cell activation to produce proliferating progenitors for regeneration.