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Blastomere Explants to Test for Cell Fate Commitment During Embryonic Development
Published on: January 26, 2013
The fate of cells undergoing spontaneous DNA damage during development
Agnes Miermont1, Vlatka Antolović1, Tchern Lenn1
1MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, London, UK.
Abstract:
Embryonic development involves extensive and often rapid cell proliferation. An unavoidable side effect of cell proliferation is DNA damage. The consequences of spontaneous DNA damage during development are not clear. Here, we define an approach to determine the effects of DNA damage on cell fate choice. Using single cell transcriptomics, we identified a subpopulation of Dictyostelium cells experiencing spontaneous DNA damage. Damaged cells displayed high expression of rad51, with the gene induced by multiple types of genotoxic stress. Using live imaging, we tracked high Rad51 cells from differentiation onset until cell fate assignment. High Rad51 cells were shed from multicellular structures, excluding damaged cells from the spore population. Cell shedding resulted from impaired cell motility and defective cell-cell adhesion, with damaged cells additionally defective in activation of spore gene expression. These data indicate DNA damage is not insulated from other aspects of cell physiology during development and multiple features of damaged cells prevent propagation of genetic error. Our approach is generally applicable for monitoring rare subpopulations during development, and permits analysis of developmental perturbations occurring within a physiological dynamic range.
Insights
DNA damage during embryonic development causes cell shedding, preventing damaged cells from forming spores. This study identifies a method to track these rare cells and understand developmental impacts.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Embryonic development involves rapid cell proliferation, which can lead to DNA damage.
- The impact of spontaneous DNA damage on cell fate during development is not well understood.
Purpose of the Study:
- To develop an approach for identifying and analyzing the effects of DNA damage on cell fate decisions during development.
- To investigate the physiological consequences of DNA damage in a developing multicellular organism.
Main Methods:
- Utilized single-cell transcriptomics to identify cells with spontaneous DNA damage.
- Employed live imaging to track the developmental trajectory of high Rad51-expressing cells.
- Assessed cell motility, cell-cell adhesion, and gene expression in damaged cells.
Main Results:
- Identified a subpopulation of Dictyostelium cells with spontaneous DNA damage, characterized by high Rad51 expression.
- Observed that damaged cells exhibited impaired motility and cell-cell adhesion, leading to their shedding from developing structures.
- Found that damaged cells were excluded from the spore population and showed defective spore gene expression.
Conclusions:
- Spontaneous DNA damage during development affects cell fate by causing cell shedding, thus preventing the propagation of genetic errors.
- The study presents a broadly applicable method for monitoring rare cell subpopulations and analyzing developmental perturbations.
- DNA damage is integrated with other cellular processes, influencing multiple aspects of cell physiology during development.
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