Planarian regeneration depends on a unique population of pluripotent stem cells called neoblasts. When a planarian is amputated neoblasts close to the wound respond by actively proliferating and migrating towards the wound forming the regenerative blastema in which most of the missing structures will differentiate. Although the pluripotency of the neoblasts as a whole population has been classically suggested and believed, it was in 2011 that the laboratory of Peter Reddien provided strong experimental evidence that at least a part of the neoblast population includes truly pluripotent stem cells. Thus, a single of these pluripotent neoblasts can rescue planarians lethally-irradiated (http://www.ncbi.nlm.nih.gov/pubmed/21566185).
The regenerative blastema has been classically seen as a rather uniform mass of undifferentiated cells, probably multipotent. However, recent data suggest that this could be not entirely true. In a recent hypothesis paper, Reddien discusses this possibility as well as at what stage of regeneration neoblasts and/or neoblast progeny are specified to differentiate into the required cell types (http://www.ncbi.nlm.nih.gov/pubmed/23404104). The author proposes two alternative (although not necessarily mutually exclusive) models: in the “naïve neoblast model” pluripotent neoblasts divide and migrate into the blastema where they would stop dividing and then be specified and differentiated into the proper cell types; alternatively, in the “specialized neoblast model”, there would be specialized neoblasts that would produce different lineage-committed non-dividing blastema cells. In this last case, therefore, the specification of the blastema cells towards a particular cell fate would occur somehow prior they enter the blastema. The “specialized neoblast model” is supported by the fact that at least for three different cell types: eye-pigment, photoreceptors and protonephridia, specific cell populations of progenitor-like neoblasts express specific transcription factors that specify those neoblasts towards those cell fates (http://www.ncbi.nlm.nih.gov/pubmed/21852957, http://www.ncbi.nlm.nih.gov/pubmed/21937596). Still, they are “neoblasts” according to the definition of neoblast used here: “cells expressing smedwi1 and irradiation sensitive (during the first 24h after irradiation)”.
There is no doubt that those recent findings of progenitor cells for some planarian cell types have re-opened an exciting debate on how heterogeneous are neoblasts in terms of their potentiality. As stated in Reddien’s paper many questions need to be solved, starting with a definition of a neoblast. Also, it would be important to determine up to what extend these specialized neoblasts are not only present in uninjured animals but divide and are maintained in them for regular cell turnover. If specialized neoblasts exist at low numbers in uninjured animals what happens after amputation: do naïve multipotent neoblasts make more specialized neoblasts? Do the few specialized neoblasts divide and make more of them? Or both?
Finally, as both models make an important distinction on whether blastema cells are specified within (naïve model) or outside (specialized model) the blastema, it would be then appropriate to look for a good definition of a blastema. Very often a planarian blastema is defined as the mass of unpigmented tissue that grows below the wound, but body pigmented cells differentiate relatively late so after 5 days of regeneration you have a rather unpigmented mass of cells but in fact inside a new brain, for example, has already differentiated. So, up to what stage during regeneration a blastema is a blastema? And also, how early can we talk about a blastema? Many of the important decisions such as, for example, the establishment of proper polarity are made very early after amputation, and before any sign of new tissue really appearing below the wound. And that polarity decisions are going to affect the cell types you will need; it is not the same regenerating a head with its brain than a tail. So, during regeneration, the signals that generate specialized neoblasts from naïve pluripotent neoblasts where do they come from? From pre-existing cells in the stump? When the blastema is formed, does it have any role in cell specification (in the “specialized neoblast model”)? or does it play a mere organizational role? Anyway the definition of “blastema” would probably deserve another post by itself.