The Transcriptional Biographies of Embryonic Cells
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CitationWang, Yiqun. 2021. The Transcriptional Biographies of Embryonic Cells. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
AbstractDuring metazoan development, a single totipotent cell is transformed into an organism comprised of numerous cell types with distinct structures, functions and transcriptional states. Therefore, two central questions in developmental biology have been: how are cells specified to adopt distinct fates, and how are cells remodeled during differentiation to acquire diverse features? To address these questions, we used zebrafish embryogenesis as a model system, and performed single-cell RNA sequencing (scRNA-seq) to understand the transcriptional changes underlying cell type specification and differentiation.
To reconstruct the process of cell type diversification and to define the gene expression dynamics underlying the specification of each cell type, we obtained 38,731 single-cell transcriptomes in early zebrafish embryos, from the activation of the zygotic genome (3.3 hpf) to early somitogenesis (12 hpf). Using this data, we reconstructed transcriptional trajectories in form of a branching tree, which represents the gene expression paths from a multipotent cell type to each descendant specified cell type.
To understand the cellular remodeling processes during differentiation, we focused on the transcriptional trajectories of two secretory cell types: the notochord and the hatching gland. Using gene expression dynamics and functional annotations, we identified gene modules reflecting various cellular processes during their differentiation, including the unfolded protein response (UPR). By combining genetic perturbation and scRNA-seq, we further identified the UPR pathway transcription factors (TFs) as the major regulators of common and cell type-specific secretion programs.
Our trajectory reconstruction results highlight the concurrent canalization and plasticity of embryonic specification; our gene module analysis reveals genes underlying cellular remodeling processes and their highly efficient temporal organizations; and our UPR TF analysis demonstrates their physiological role in expanding the secretion capacity of the precursors of professional secretory cells. The experimental and computation methods from our studies provide a framework to reconstruct complex developmental processes.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368449
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