Cell quiescence in planarian stem cells, interplay between p53 and nutritional stimuli

Abstract

Cell quiescence appeared early in evolution as an adaptive response to adverse conditions (i.e. nutrient depletion). In metazoans, quiescence has been involved in additional processes like tissue homeostasis, which is made possible by the presence of adult stem cells (ASCs). Cell cycle control machinery is a common hub for quiescence entrance, and evidence indicates a role for p53 in establishing the quiescent state of undamaged cells. Mechanisms responsible for waking up quiescent cells remain elusive, and nutritional stimulus, as a legacy of its original role, still appears to be a player in quiescence exit. Planarians, rich in ASCs, represent a suitable system in which we characterized a quiescent population of ASCs, the dorsal midline cord (DMC) cells, exhibiting unique transcriptional features and maintained quiescent by p53 and awakened upon feeding. The function of DMC cells is puzzling and we speculate that DMC cells, despite retaining ancient properties, might represent a functional drift in which quiescence has been recruited to provide evolutionary advantages.

Starvation resistance in planarians: multiple strategies to get a thrifty phenotype

“…In our previous paper, we demonstrated that the interplay between p53 and nutritional stimuli regulates planarian stem cell quiescence [23] and additional literature data support that the ancestral activity for which p53 was selected for, is related to stem cell biology [24–27]. This is also true for planarian in which Smed‐p53 is not involved in the response to genotoxic stress [28].…”

“…A special mention should be dedicated to Djp53 , which in D. japonica is enriched in the stem cell compartment [23]. Djp53 is an antiproliferative factor [23] and its downregulation in a fasting regimen might be consistent with the ability of planarians to maintain a constant bmi.…”

“…A special mention should be dedicated to Djp53 , which in D. japonica is enriched in the stem cell compartment [23]. Djp53 is an antiproliferative factor [23] and its downregulation in a fasting regimen might be consistent with the ability of planarians to maintain a constant bmi. Indeed, in starving regimen, if on the one hand, the reduction of cell energy hinders stem cell propensity to divide, on the other hand, the concomitant reduction of an anti‐proliferative factor plausibly promotes cell proliferation, thus suggesting that the ratio between cell energy and Djp53 expression is crucial in deciding stem cell fate.…”

“…According to our data, Djp53 is negatively regulated in fasting condition while DjsoxP1 shows a reduction trend. This is particularly intriguing because, 972 in D. japonica, Djp53 and DjsoxP1 transcription factors are both present in the stem cell compartment [23] and play an antagonistic effect, being the first an antiproliferative factor and the second involved in stem cell self-renewal and required in the rescue process after low-dose X-ray treatment for colony expansion [21]. This prompted us to analyze the trend of the expression level of these two transcription factors early after feeding, in way to provide further validation of the correlation between Djp53 expression and nutritional status.…”

“…Dissociated/fixed cells were suspended in PBS plus 1% bovine serum albumin and stained with anti-pS10H3 FLUO antibody (1 : 50 dilution) (06-570-AF488 Merck, EMD Millipore Corp., Burlington, MA, USA) and propidium iodide following the protocol described byGambino et al [59]. Stained cells were visualized using an ACCURI C6 PLUS (BD Biosciences, Franklin Lakes, NJ, USA) cytofluorimeter by setting doublets discrimination, gating and data quantification according to Gambino et al[23]. A minimum of 10 000 events were acquired in five independent samples for each experimental condition.…”