Molecular and Behavioural Differences Between Homeostatic and Growth Stem Cells

• Applicant: Professor Lazaro Centanin, Ph.D.
• Subject Area: Developmental Biology ; Cell Biology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446329887

Adult stem cells are involved in the homeostatic replacement of cells that mammals lose as a part of their normal biological activity. In teleost fish stem cells also drive constant organismal growth, either by generating new cells that are integrated into a functional organ or by producing organs that are integrated into a functional system. We have been developing genetic tools in medaka fish (Oryzias latipes) to interrogate the behaviour of adult stem cells focusing on whether the same stem cell is responsible for both growth and homeostasis or if alternatively, these tasks rely on different populations with specific features.Recent work from my group has already identified growth and homeostatic stem cells using the fish gill (1), a largely unexplored organ that displays both a high cellular turnover rate and massive post-embryonic growth. This proposal aims at tackling these two populations molecularly, by performing deep RNAseq on growth and homeostatic stem cells to mechanistically uncover their similarities and differences. Additionally, we will challenge fish with different environmental conditions that are reported to impact on the relative cellular composition of the gill, to address whether the physiological responses to external stimuli (plasticity) are mediated by growth or homeostatic stem cells.We hypothesise that in animals with fixed adult size, including mammals, aSCs are restricted to the homeostatic function. Uncovering experimental conditions that turn homeostatic stem cells into growth stem cells, and characterising the molecular fingerprints of each state will impact on our understanding of pathological cases that result from aSC driven growth.

• DFG Programme: Research Grants