Asymmetric Cell Division Mechanisms in Stem Cells

Asymmetric cell division underpins the capacity of stem cells to balance self-renewal with differentiation by generating two daughter cells with distinct fates. Central to this process is the establishment of cell polarity, whereby conserved polarity complexes localise to define apical and basal domains. The mitotic spindle aligns according to these cues to ensure faithful segregation of genetic and cytoplasmic determinants. Concurrently, the cortical actomyosin network and associated flows adjust membrane tension and curvature, guiding the site of cleavage furrow ingression. Regulatory kinases and phosphatases modulate the localisation of fate determinants through phosphorylation cycles and scaffold interactions, while mechanical feedback from the microenvironment via mechanotransduction pathways further shapes division outcomes. Disruption of these mechanisms can compromise tissue homeostasis, leading to developmental defects or tumourigenesis. Advances in live-cell imaging, optogenetics and biomaterials have elucidated how temporal coordination of biochemical and biophysical processes achieves robust asymmetry. A detailed understanding of these mechanisms holds promise for therapeutic strategies in regenerative medicine, cancer biology and organogenesis by informing the engineering of stem cell behaviour and tissue architecture.

Research from Nature Portfolio

Recent studies have shown that polarised branched actin modulates cortical mechanics to produce daughter cells of unequal size through regulation of cortical bending rigidity and curvature in sensory organ precursors. Optogenetic manipulation of actin nucleation has revealed how temporal control of actin distribution dictates cleavage furrow placement. A foundational investigation in Drosophila neural stem cells established that spatiotemporal cortical flows of myosin, in concert with spindle geometry, define the site of furrow ingression and physical asymmetry. This work elucidates how polarity cues and spindle-dependent signals interface to ensure precise partitioning of fate determinants during cytokinesis.

Asymmetric Cell Division Mechanisms in Stem Cells publication trend

The graph below shows the total number of articles in asymmetric cell division mechanisms in stem cells across all publications each year (not limited to Nature Index journals).

Technical terms

Asymmetric cell division: The process by which a stem cell divides to produce two daughter cells with distinct sizes, compositions or fates.

PAR polarity complex: A set of evolutionarily conserved proteins that localise asymmetrically to establish and maintain cell polarity.

Cortical flows: Directed movements of the cell cortex induced by actomyosin contractions, redistributing polarity factors.

Actomyosin: The combined network of actin filaments and myosin motors that generate contractile forces at the cell cortex.

Mitotic spindle: A microtubule-based structure that segregates chromosomes and influences cleavage furrow positioning.

Mechanotransduction: The conversion of mechanical cues from the microenvironment into intracellular biochemical signals.

Cleavage furrow: The indentation formed at the cell equator that deepens to separate two daughter cells during cytokinesis.

References

1. Polarized branched Actin modulates cortical mechanics to produce unequal-size daughters during asymmetric division. Nature Cell Biology (2023).
2. Spatio-temporally separated cortical flows and spindle geometry establish physical asymmetry in fly neural stem cells. Nature Communications (2017).
3. Using biomaterials to study stem cell mechanotransduction, growth and differentiation. Journal of Tissue Engineering and Regenerative Medicine (2014).
4. Asymmetric recruitment and actin-dependent cortical flows drive the neuroblast polarity cycle. eLife (2019).
5. aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts. eLife (2018).