The role of centrioles and cilia in asymmetric neural stem cell division

Control of stem cell division modes is important to ensure generation of properly sized tissues during development as well as adult tissue homeostasis and repair. Stem cells undergo repeated cell divisions in which they produce daughter cells that either mature or remain stem cells. Surprisingly, the number and type of produced daughter cells vary between individual stem cells. To understand this heterogeneity better, my group is investigating how stem cells, and in particular neural stem and progenitors, are regulated at the single-cell level.

Asymmetric stem cell divisions balance stem cell self-renewal and differentiation as the mother cell gives rise to two unequal daughter cells. These different fates can be induced by unequal segregation of organelles and cell fate determinants between daughter cells. I previously showed that membrane derived from primary cilia, which are key sensory organelles, is retained by one of the centrosomes throughout mitosis by neural stem cells. This ciliary membrane remnant is inherited mainly by the stem cell daughter cell that re-establishes a cilium before its sister cell. We propose that the observed asynchronous ciliogenesis after mitosis differentially exposes daughter cells to proliferative signals and influences downstream cell fate decisions.

My research group is currently developing and applying state-of-the-art single-cell analyses, time-lapse imaging and genetic manipulations to investigate stem cell decisions in zebrafish and mouse embryos. These approaches are complemented with computational modelling to predict the effects of gene expression and signalling activity changes on stem cell division outcomes. Unravelling the mechanisms that regulate stem cell decisions could provide new insights and means to manipulate stem cells to aid tissue regeneration and healthy ageing.