Abstract
Under physiological conditions, the complex planarian neoblast system is a composite of hierarchically organized stem cell sub-populations with sigma-class neoblasts, including clonogenic neoblasts, endowed with larger self-renewal and differentiation capabilities, thus generating all the other sub-populations and dominating the regenerative process. This complex system responds to differentiated tissue demands, ensuring a continuous cell turnover in a way to replace aged specialized cells and maintain tissue functionality. Potency of the neoblast system can be appreciated under challenging conditions in which these stem cells are massively depleted and the few remaining repopulate the entire body, ensuring animal resilience. These challenging conditions offer the possibility to deepen the relationships among different neoblast sub-populations, allowing to expose uncanonical properties that are negligible under physiological conditions. In this paper, we employ short, sub-lethal 5-fluorouracil treatment to specifically affect proliferating cells passing through the S phase and demonstrate that S-phase slowdown triggers a shift in the transcriptional profile of sigma neoblasts, which reduces the expression of their hallmark sox-P1. Later, some cells reactivate sox-P1 expression, suggesting that some neoblasts in the earlier steps of commitment could modulate their expression profile, reacquiring a wider differentiative potential.
Highlights
IntroductionThe planarian stem cell system, composed of sub-populations endowed with different self-maintenance, replicative, and differentiation potential, offers a unique opportunity to study the complex cross talk among stem cells themselves and between stem cells and differentiated cell compartments in an in vivo context
Planarians are resilient to low-dose 5FU treatment, and DjsoxP-1 In sigmacontrast, DjpiwiA- and DjCIP29-positive cells reduce in number slower than DjsoxP-1high oblasts reappear afterand initial sterilization and repopulate the planarian body cells, never[5,20]
The still high dUTP/dTTP ratio most probably leads to frequent miss-incorporation of dUTP into the de-novo-synthesized DNA strand [33]
Summary
The planarian stem cell system, composed of sub-populations endowed with different self-maintenance, replicative, and differentiation potential, offers a unique opportunity to study the complex cross talk among stem cells themselves and between stem cells and differentiated cell compartments in an in vivo context. Planarian stem cells are referred to as neoblasts and share ultrastructural features, the ability to proliferate, and hallmarks in their transcriptional profile [1]. Neoblasts are involved in tissue homeostasis in intact organisms and, during regeneration, proliferate and accumulate below the wound, producing a blastema, where the missing body structures are reformed [2]. Among the different neoblast specific genes identified so far, Schmidtea mediterranea smedwi1 [3] and its Dugesia japonica homologue DjpiwiA [4] are the most recognized markers to label a cell as a neoblast at present
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