Rethinking differentiation: stem cells, regeneration, and plasticity

Abstract

Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations, are beginning to erode many of these established concepts and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process.

Figure 1. Potency, reprogramming and differentiation

Discoveries and technological breakthroughs associated with the concept of cellular differentiation. The background image is plate 37 from Haeckel’s Kunstformen der Natur (Haeckel, 1904) and depicts a siphonophore.

Figure 2. Biological adaptations of stem cell functions

A) The evergreen perennial plant Azorella compacta grows constitutively through the continuous proliferation and differentiation of its meristem stem cells (Credit: Pedro Szekely (http://commons.wikimedia.org/wiki/File:3,000_Year_Old_Yareta_Plant_%282087602585%29.jpg). B) The colonial ascidian Botryllus schlosseri regenerates its whole body almost weekly as part of its sexual and asexual reproductive strategy (Credit: Parent Géry (http://commons.wikimedia.org/wiki/File:Botryllus_schlosseri_%28Pallas,_1766%29_.jpg). C) The negligibly senescent planarian Schmidtea mediterranea is a constitutive adult which constantly replaces dying differentiated cells with the freshly minted progeny of its abundant stem cell population (Credit: Erin Davies).

Figure 3. Demonstration of pluripotency of blastomeres in siphonophores

Dissection of siphonophore larvae in half (Fig. 73 and 74 in plate). The same larvae halves a few hours after physical separation (Figs. 75 and 76 in plate). Larvae separated into thirds 8 days after dissection (Figs. 77, 78 and 79). Figures 77 and 79 illustrate larvae fragments that developed an air sac and polyps (Fig. 77) and a normal, full larvae (Fig. 79). Finally, Figs 80, 81, 82, and 83 illustrate the results of quartering siphonophore larva with only 83 developing normally (Haeckel, 1869).

Figure 4. Pioneering work of Ethel Browne Harvey demonstrating the ability of transplanted tissues to reprogram the fate of host cells

Reproduced from the original (Browne Harvey, 1909), this image illustrate the specific outcomes of transplanting of various body parts between pigmented (green) and unpigmented strains of Hydra. Fig. 42: Graft of white tentacle with peristome in middle of green hydra. Fig. 43: Graft of white tentacle with peristome in foot of green hydra. Fig. 44: Graft of green tentacle without peristome in white hydra. Fig. 45: Graft of green body tissue in white hydra. Fig. 46: Graft of green hydranth in white hydra. Fig. 47: Graft of green foot in white hydra. Fig. 48: Heteromorphosis in reversed ring of green tissue grafted on white stock.

Figure 5. Animals reported of being capable of reverse development

A) Turritopsis dohrnii. B) Laodicea undulate (Credit for both images: Alvaro A. Migotto http://cifonauta.cebimar.usp.br/photo/2190/ and http://cifonauta.cebimar.usp.br/photo/10792/).