Pathogenicity of Entamoeba Species Depends on Cell Line Conversion,Genome Reprogramming and Epigenetic Gene Regulation

The protist life cycle is certainly much more than a simple sequence of trophic and non-trophic stages (cysts), and trophic cells (trophozoites) do not divide categorically into two identical daughter cells. The pathogenic amoebae Entamoeba histolytica and Entamoeba invadens exhibit complex life cycles including stem cells and cell lines following various biological tasks such as virulence and encystment. Intrinsic and extrinsic molecular mechanisms controlled by environmental cues, develop in both species a PST stem cell lineage that consists of primary, secondary and tertiary self-renewing cell lines. Oxygen gradients controlled by the host intestine and bacteria initiate the stem cell lineage machinery and are responsible for cell line conversions. Entamoeba dispar has a similar PST stem cell lineage despite being less pathogenic. These three amoebic species begin their life cycle with a primary multipotent stem cell line (p-SRL) that starts from metacystic amoebulae. The p-SRL line converts to progenitor cell lines depending on the environmental oxygen content. Progenitor cell lines are of reduced potency. The secondary s-SRL line produce mitotic arrested MAS cells (cyst precursor cells) committed for terminal differentiation; they continue development entering the endopolyploid cell cycle, a developmental cycle opponent to mitosis and form cysts. The tertiary t-SRL line does not form cysts. It produces mitotic quiescent MAT cells that enter a state of G0 and mature to invasive cells of variable genotypic virulence. MAT cells reentering mitotic cycle form new t-SRL variants. In hypoxic conditions the t-SRL line changes to symmetric cell fate