Periodic Reporting for period 3 - NeuroStemCircuit (Neural Circuit Regulation of Adult Brain Stem Cells)
Reporting period: 2021-10-01 to 2023-03-31
Stem cells are found in the adult brain and reside in specialized microenvironments that support them throughout life. Adult brain stem cells are very diverse. They are found in dormant and actively dividing states, and, depending on their location they generate different types of neurons and glial cells. However, the signals that control these different pools of stem cells, and why there are so many different types of stem cells is unclear. We will explore whether different physiological states regulate distinct pools of stem cells in the adult brain, and whether these differ in males and females. We will also define how long-range signals dynamically change and regulate distinct pools of stem cells in different states. Together these will provide key insight into the logic underlying stem cell diversity and how different stem cells integrate signals from remote brain areas, and contribute to brain plasticity. They may ultimately inform how endogenous stem cells can potentially be harnessed for brain repair, or become altered in disease states.
In the first period of the project, we have identified new glial cell types and stem cell domains in the brain. We have found that pregnancy results in the choreographed recruitment of different pools of stem cells to become active, leading to the generation of specific types of neurons and glia during motherhood. We have uncovered different compartments of the niche that regulate these processes, including important differences between male and females.
This interdisciplinary project lies at the interface of stem cell biology and neuroscience. We have found that different physiological states recruit distinct pools of adult neural stem cells in the adult brain to become activated and generate specific types of neurons and glia “on-demand” in anticipation of physiological need.
We are using multi-pronged approaches to investigate diverse stem cell responses to different stimuli from the single cell to whole organism level, and developing novel tools to map stem cell dynamics. Together, this project will uncover how physiological states are sensed and relayed to the adult neural stem cell niche and shed light on the functional significance of adult neural stem cell heterogeneity in males and females.
We are using multi-pronged approaches to investigate diverse stem cell responses to different stimuli from the single cell to whole organism level, and developing novel tools to map stem cell dynamics. Together, this project will uncover how physiological states are sensed and relayed to the adult neural stem cell niche and shed light on the functional significance of adult neural stem cell heterogeneity in males and females.