A. Top, stem cells self-renew and produce one or more differentiated cells. Middle, dedifferentiation is the process by which a cell loses differentiated character to produce a progenitor cell that can divide to produce more differentiated cells. Bottom, transdifferentiation involves the change of one cell type into others. This could occur without division, or following de-differentiation of one cell type into a progenitor for additional cell types. B. Distinct ways for accomplishing tissue-level pluripotency. Left, a pluripotent progenitor cell (a stem cell is depicted) produces differentiated progeny cells spanning multiple germ layers. There could exist multiple, and/or self-renewing intermediates along different lineage paths. Right, different lineage-restricted progenitor cells (stem cell types are depicted) each produce different differentiated cells. Each different tissue separately generates or harbors a restricted stem cell. These stem cells together can reconstitute the three different tissues, while any individual on its own is not sufficient.

A. Neoblasts (blue), are the somatic dividing cells of planarians and are depicted in blue. Neoblasts are scattered throughout the body, but restricted to behind the eyes and absent from the pharynx (centrally located). B. Irradiation with 1,750 rad can result in animals with a single surviving neoblast. This single cell can divide and produce a colony of neoblasts, ultimately producing differentiated cells spanning germ layers (). For example, individual neoblasts can generate both neurons and intestine cells, as well as defined neoblast progeny populations. C. Irradiation with 6,000 rad eliminates all neoblasts. Transplant of a single cNeoblast from a donor strain (red) results in clonogenic growth and, ultimately, the restored capacity for regeneration.

A. Hydra are cnidarians with a primary body axis containing a hypostome (or head) at one end and a foot at the other. Cell proliferation in the body column continually pushes cells to the poles of the body. Asexual reproduction is accomplished by budding. B. The body wall contains two epithelial cell layers, ectodermal and endodermal epithelial cells. Interstitial stem cells exist within the ectodermal epithelial cell layer. C. The ectodermal and endodermal epithelial cells proliferate continuously to maintain these tissue layers, producing differentiated epithelial cells, and are therefore considered to be distinct stem cells. A third stem cell type, the multipotent, interstitial stem cell can self-renew and produce neurons, nematocytes, secretory cells, and gametes.

Cell labeling was primarily achieved via grafting of embryonic tissues during the neurula stage from GFP-expressing donors to normal hosts. (Top) Xenopus: posterior neural plate, presomitic mesoderm, and notochord were transplanted to label tail spinal cord, muscle, and notochord, respectively. After tail amputation, the labeled tissues regenerated the same tissue type as prior to amputation (). (Bottom) Axolotl limb Schwann cells and muscle were labeled by embryonic presomitic mesoderm and neural crest transplantation (). Dermis and cartilage were labeled by direct tissue transplantation in the limb, as well as embryonic tissue grafts (). After limb amputation, labeled Schwann cells regenerated Schwann cells only. Muscle regenerated muscle and no cartilage. Dermis regenerated dermis, cartilage and connective tissues (also described by ), while cartilage regenerated cartilage (also described by ).

A. Prior to heart resection, cardiomyocytes were labeled via a cardiomyocyte-specific promoter driving the CreER sequence. CreER acted on a cardiomyocyte-specific loxP reporter where a floxed STOP cassette was excised by CreER, which is active in the presence of 4-HT (4-hydroxytamoxifen), to induce GFP expression. Newly regenerated cardiomyocytes (right, below dotted line) express GFP, indicating that they derived from cardiomyocytes in the injured heart tissue (; ). B. Tracking of osteoblasts during caudal fin regeneration demonstrates that they contribute to the regenerated fin and remain restricted to an osteoblast identity. osterix:Cre-ERT2 acting on the loxP reporter; upon Cre-mediated excision of a STOP cassette, the hsp70 promoter drives expression of GFP. GFP expression was induced prior to fin amputation leading to sporadic cell labeling. GFP-expressing cells generate osteoblasts in the regenerated fin, indicating that osteoblasts de-differentiated and divided to produce more osteoblasts, remaining restricted to the osteoblast fate during regeneration ().