Cell-to-cell interactions in EML cell differentiation: The role of diversity and heterogeneity in cell populations
Date
2013-05-27
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Abstract
The differentiation of hematopoietic stem cells to mature cell types is a multistep, branching process that generates the various cell types of the entire blood system. Our laboratory and others recently found that the heterogeneity of cell phenotypes that is present even in a clonal population of nominally identical cells plays a central role in cell fate choice and commitment of multi-potent progenitor cells. In this project I analyzed the precise dynamics of such cell population heterogeneity during differentiation and asked whether there is a specific heterotypic communication between the cells given that individual cells exhibit distinct behaviors. For this purpose I examined cell fate commitment of the hematopoietic progenitor cell line EML into the myeloid lineage at single-cell resolution using flow cytometry to monitor the induction of the differentiation marker, CD11. First I found that individual EML cells of a clonal cell population begin the differentiation process at disparate time points despite the simultaneous stimulation of differentiation and the uniformity of the culture environment. This asynchrony suggests an intrinsic heterogeneity also with respect to the response kinetics which further increases the diversity of the cells. Specifically, dissection of this differentiation process along the CD11b axis revealed that the differentiating signal led to a splitting of the uniform population into three discrete subpopulations at an intermediate stage. Second, I found that all three subpopulations were necessary to sustain a maximal differentiation rate of the entire population. Thus these subpopulations do not act independently but instead, communicate with each other. I determined that this communication is mediated via soluble signals and that it significantly affected the global differentiation kinetics of population. Finally, I have also begun to identify the nature of the soluble factor that mediates this interaction and discovered that production of IFN-γ during myeloid differentiation accelerates the process. These observations indicate that differentiation of a uniform cell population of cells from a precursor state to a mature state involves a non-cell-autonomous behavior that is mediated by secreted factors.
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Biology--Cell
Citation
Gomez-castano, I. (2013). Cell-to-cell interactions in EML cell differentiation: The role of diversity and heterogeneity in cell populations (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25236