Biophysical properties regulating neural stem cell quiescence

Dr Rita Sousa-Nunes (primary)
Centre for Developmental Neurobiology (CDN)
King’s College London
Dr Yanlan Mao (secondary)
MRC Laboratory for Molecular and Cell Biology
University College London (UCL

Abstract

Control of stem cell quiescence is essential for tissue development, homeostasis and repair; cancer; and, in the adult CNS, also learning, memory and mood. Quiescence consists of reversible cell-cycle arrest accompanied by low biosynthetic activity, which protects cells from environmental insults, replicative exhaustion and proliferation-induced mutations[1]. Despite its importance, quiescence remains poorly understood. We propose to investigate the function of two evolutionarily conserved properties of NSCs as they transition between quiescent and active states: morphological changes and mitotic somatic translocation. Our focus will be on how alterations in biophysical properties mediate NSC transitions between quiescent and active states.


References

1. Valcourt JR, Lemons JMS, Haley EM, Kojima M, Demuren OO, Coller HA. Staying alive: Metabolic adaptations to quiescence. Cell Cycle 11:1680-96, 2012.

2. Sousa-Nunes R, Lee LL, Gould AP. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila.
Nature 471:508-12, 2011.

3. Rossi A, Coum A, Madelenat M, Harris L, Miedzik A, Strohbuecker S, Chai A, Fiaz H, Chaouni R, Grey W, Bonnet D, Hamid F, Makeyev EV, Faull P, Snijders AP, Kelly G, Guillemot F, Sousa-Nunes R. Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence, bioRxiv doi.org/10.1101/2021.01.06.425462. Preprint.

4. Hunter GL, He L, Perrimon N, Charras G, Giniger E, Baum B. A role for actomyosin contractility in Notch signaling. BMC Biol 17:12, 2019.

5. Kirkland NJ, Yuen AC, Tozluoglu M, Hui N, Paluch EK, Mao Y. Tissue mechanics regulate mitotic nuclear dynamics during epithelial development. Curr Biol 30:2419-32.e4, 2020.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyNeurobiology
Techniques & Approaches
BiophysicsEngineeringGeneticsImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling