Oxygen fluctuations, adult stemness, and phenotypic change – in normal and transformed cells and tissues
Geobiological research demonstrates that oxygen-sensing mechanisms – like HIFs – had a significant role in the evolution of complex multicellularity on Earth. Thus, we aim to clarify of HIF-2α 's role in stemness in both vertebrates and invertebrates under situations of oxygen fluctuation and pseudohypoxia. This study will explore how oxygen fluctuations relate to phenotypic responses (epigenetic and genetic) in cells and how the pseudo hypoxic phenotype regulates adult stem cells pools in normal tissue. We will separate between phenotypic responses that can be described as stress responses (forming e.g., polyploidy) and those that lead to differences in phenotypic specialization and evolvability. The findings will influence our understanding of stem cell biology and cancer cell evolvability.