Abstract
Multicellular organisms contain various differentiated cells. Fate determination of these cells remains a fundamental issue. The cellular slime mold Dictyostelium discoideum is a useful model organism for studying differentiation; it proliferates as single cells in nutrient‐rich conditions, which aggregate into a multicellular body upon starvation, subsequently differentiating into stalk cells or spores. The fates of these cells can be predicted in the vegetative phase: Cells expressing higher and lower levels of omt12 differentiate into stalk cells and spores, respectively. However, omt12 is merely a marker gene and changes in its expression do not influence the cell fate, and determinant factors remain unknown. In this study, we analyzed cell fate determinants in the stalk‐destined and spore‐destined cells that were sorted based on omt12 expression. Luciferase assay demonstrated higher levels of intracellular ATP in the stalk‐destined cells than in the spore‐destined cells. Live‐cell observation during development using ATP sensor probes revealed that cells with higher ATP levels differentiated into stalk cells. Furthermore, reducing the ATP level by treating with an inhibitor of ATP production changed the differentiation fates of the stalk‐destined cells to spores. These results suggest that intracellular ATP levels influence cell fates in D. discoideum differentiation.
Highlights
Multicellular organisms consist of a variety of differentiated cells, and their differentiation processes must be tightly regulated to ensure their proper functions; errors that occur during the differentiation process may induce fatal defects in organisms
Because metabolism has been speculated to be associated with cell fate determination, in both D. discoideum (Kimura, Kuwayama, Amagai, & Maeda, 2010; Leach et al, 1973; Matsuyama & Maeda, 1995; Tasaka & Takeuchi, 1981; Thompson & Kay, 2000) and mammalian cells (Cho et al, 2006; Takubo et al, 2013), we focused on genes associated with metabolic pathways
The results demonstrated that 210 genes, corresponding with approximately 70% of the selected 304 metabolism-related genes, showed higher expression levels in stalk-destined cells than in spore-destined cells (Data set S2)
Summary
Multicellular organisms consist of a variety of differentiated cells, and their differentiation processes must be tightly regulated to ensure their proper functions; errors that occur during the differentiation process may induce fatal defects in organisms. At the beginning of the cell differentiation process, different cell types appear stochastically within a genetically identical cell population, which is known as the “salt and pepper” model and has been observed in various organisms, such as nematode worms, flies and mice (Chazaud, Yamanaka, Pawson, & Rossant, 2006; Miller, Seymour, King, & Herman, 2008; Schnabel et al, 2006) In such stochastic differentiation, non-genetic cellular heterogeneity, which arises from fluctuations of intrinsic and extrinsic factors, appears to be a key factor in the determination of cell fates. Previous studies have reported that cell differentiation can be regulated by the presence or absence of glucose, which is an essential component of the glycolysis pathway, in the culture medium (Leach et al, 1973; Tasaka & Takeuchi, 1981; Thompson & Kay, 2000) These factors generating heterogeneities reflect cell conditions in the vegetative phase, implying that cell lineages are determined prior to differentiation according to the heterogeneities present in the vegetative phase. We investigated roles of ATP in D. discoideum differentiation by using specific inhibitors of ATP production
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