Three-dimensional geometry controls division symmetry in stem cell colonies.

Area of Science:

• Cell Biology
• Developmental Biology
• Biophysics

Background:

• Spindle positioning dictates cell division orientation and symmetry, crucial for development.
• While studied in 2D, mechanisms controlling spindle positioning in 3D remain largely unknown.
• NuMA (NUMA1) orients division along the cell's long axis in 2D epithelial cells.

Purpose of the Study:

• Investigate how cells control spindle positioning and division in 3D environments.
• Utilize mouse embryonic stem cells (ESCs) in 3D colonies as a model system.
• Examine how cell geometry and cell-cell contacts influence division in 3D.

Main Methods:

• Live-cell imaging of mouse ESCs in 3D colonies.
• Analysis of spindle positioning, cell shape, and protein distribution (E-cadherin, NuMA).
• Observation of cell division symmetry and orientation during differentiation.

Main Results:

• ESCs at the periphery of 3D colonies exhibit high spindle mobility and asymmetric division.
• Unequal distribution of E-cadherin between daughter cells contributes to enhanced spindle movements.
• As ESCs differentiate, division becomes more symmetric with elongated metaphase shapes and increased cortical NuMA.

Conclusions:

• Cellular geometry and neighbor contacts in 3D environments regulate division orientation and symmetry.
• Spindle positioning control differs significantly between 2D and 3D contexts.
• E-cadherin and NuMA play roles in modulating division in 3D, particularly during differentiation.