Sub-Lethal 5-Fluorouracil Dose Challenges Planarian Stem Cells Promoting Transcriptional Profile Changes in the
Gaetana Gambino1, Chiara Ippolito1, Monica Evangelista2
1Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
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.
Insights
Planarian stem cells, called neoblasts, normally maintain tissues. Under stress, sigma neoblasts shift gene expression, revealing hidden regenerative potential.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Planarian neoblasts are hierarchically organized stem cells crucial for regeneration.
- Sigma-class neoblasts possess extensive self-renewal and differentiation capabilities.
- Neoblasts ensure tissue homeostasis and replace aged cells.
Purpose of the Study:
- To investigate neoblast sub-population dynamics under stress.
- To explore uncanonical stem cell properties revealed by challenging conditions.
- To understand how sigma neoblasts respond to S-phase perturbation.
Main Methods:
- Utilizing short, sub-lethal 5-fluorouracil treatment to induce S-phase stress.
- Analyzing transcriptional profile shifts in sigma neoblasts.
- Monitoring the expression of the hallmark gene sox-P1.
Main Results:
- Sub-lethal 5-fluorouracil treatment caused a slowdown in S-phase progression.
- Sigma neoblasts exhibited reduced expression of sox-P1 following treatment.
- Some neoblasts later reactivated sox-P1 expression, indicating potential plasticity.
Conclusions:
- S-phase stress can alter the transcriptional profile of sigma neoblasts.
- Neoblasts may modulate their differentiation potential in response to environmental cues.
- This plasticity offers insights into stem cell behavior and regeneration.
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