WEHI PhD Completion Seminar hosted by Professor Shalin Naik

Esmaeel Azadian
PhD Student – Nail Laboratory, Immunology division, WEHI

Clonal Destiny: How Cells Program Their Growth Fate 

L7W Seminar Room

Join via TEAMS

Including Q&A session

Not all cell divisions are equal. Even among seemingly genetically identical cells, growth rates of individual cells and their daughters (clones) can differ and responses to the environment are far from uniform. In this way, some clones grow more than others, whether in tissues or in a culture flask. The long-standing assumption has been that this variation is stochastic biological noise inherent to cell division. But what if it reflects something more structured? 

In my PhD, I tracked the kinetics of thousands of individual clones over long timescales across two biologically distinct systems: human breast cancer cells (MDA-MB-231) and normal dermal fibroblasts. Through cellular barcoding and clone splitting, sibling cells were tracked in separate culture flasks in vitro over several months. The rationale was straightforward: if the kinetics of cell generation were concordant between flasks, the growth program was imprinted in the founder cell and heritable to daughters; if not, variation was stochastic. Across both systems, clonal kinetics were remarkably concordant, demonstrating that growth properties are stable, heritable, and clone-intrinsic. Integrating clonal kinetics with transcriptome profiling of their siblings early during the culture process further identified gene expression programs prospectively explaining clonal growth properties both in vitro and in vivo. Moreover, for the breast cancer cell line, metastatic dissemination was also a clone-intrinsic feature. Candidate regulators of clonal growth were not obvious through single cell analysis alone and I developed a pipeline to extract these hidden predictors of clonal behaviour. These are currently being tested for causation through CRISPR-based perturbation screening. 

These findings challenge the prevailing view that cellular heterogeneity is mere noise. If growth fate is heritable, a cell population’s trajectory may be written long before it is observed - making heterogeneity not something to discount, but important structured variation with broad biological implications. By establishing clonal destiny of growth as a fundamental principle of dividing cell populations, this study reveals something that may have been hiding in plain sight across decades of cell biology. 

All welcome!