Neural Circuit Regulation of Adult Brain Stem Cells

Project Information

NeuroStemCircuit

Grant agreement ID: 789328

DOI

10.3030/789328

Project closed

EC signature date 6 June 2018

Start date 1 October 2018

End date 31 March 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 499 833,00

EU contribution

€ 2 499 833,00

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 4 - NeuroStemCircuit (Neural Circuit Regulation of Adult Brain Stem Cells)

Reporting period: 2023-04-01 to 2025-03-31

Summary of the context and overall objectives of the project

Stem cells are found in the adult brain and reside in specialized microenvironments that support them throughout life. Adult brain stem cells give rise to different types of neurons and glia depending on their spatial location. Moreover, many are found in a dormant state. Understanding the signals that control different sets of stem cells will inform how endogenous stem cells contribute to brain plasticity, and ultimately how they can potentially be harnessed for brain repair, or become altered in disease. The goal of this research project is to uncover whether different physiological states regulate specific pools of stem cells in the adult brain, illuminate molecular differences among stem cells, and to define the long-range signals that dynamically change and regulate distinct pools of stem cells in different contexts.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Our project has made key progress in understanding the functional significance of adult neural stem cell diversity. We have identified new glial cell types and stem cell domains in the brain, as well as molecular regulators of these cells. We have found that reproductive states, including pregnancy, results in the choreographed recruitment of multiple different pools of stem cells to become active, leading to the generation of specific types of transient neurons and glia during motherhood that are important for maternal behaviour. We have also identified long-range neural circuits and the choroid plexus as key mediators and sources of signals of the recruitment of regionally distinct stem cells in different physiological states. Together our findings provide novel insight into the logic underlying stem cell diversity and how different stem cells integrate signals from remote brain areas, and contribute to brain plasticity.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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 have used multi-pronged approaches to investigate diverse stem cell responses to different stimuli from the single cell to whole organism level, and developed novel tools to map stem cell dynamics. Together, this project has shed light on the functional significance of adult neural stem cell heterogeneity and uncovered how physiological states are sensed and relayed to the adult neural stem cell niche.

Intraventricular oligodendrocyte progenitor (green) contacting axons (red). Nuclei are blue