Measuring and understanding interactions across temporal and spatial scales in multicellular tissues
- This thesis includes work in two distinct yet connected areas, focusing on biological interactions across temporal and spatial scales in multicellular tissues. First, I develop a method to improve the resolution and capture efficiency of spatial transcriptomics. Second, I combine approaches of molecular and cellular studies with physical modeling to investigate systemic wound responses during whole-body regeneration in planarian. In the first part, we significantly improve the performance of capture array-based spatial transcriptomics, which is commonly used to analyze gene expression in diverse tissue contexts. Its spatial resolution is currently limited by the density of the barcoded arrays. To overcome this, we introduce Expansion spatial transcriptomics (Ex-ST), a method that involves clearing and expanding the tissue before capturing the entire polyadenylated transcriptome using an enhanced protocol. This approach allows us to achieve higher spatial resolution and capture efficiency which we demonstrate using mouse brain samples. In the second part, we examine the distant responses induced by injury, the functions and mechanisms of which remain largely unknown. Using planarian flatworms capable of whole-body regeneration, we report that injury induces Erk activity wave to travel at a speed 10-100 times faster than those in other multicellular tissues. This ultrafast propagation requires longitudinal body-wall muscles, elongated cells forming dense parallel tracks running the length of the organism. The morphological properties of muscles allow them to act as superhighways for propagating and disseminating wound signals. Inhibiting Erk propagation prevents tissues distant to the wound from responding and blocks regeneration, which can be rescued by a second injury to distal tissues shortly after the first injury. Our findings provide a mechanism for long-range signal propagation in large complex tissues to coordinate responses across cell types and highlight the function of feedback between spatially separated tissues during whole-body regeneration.
|Type of resource
|electronic resource; remote; computer; online resource
|1 online resource.
|Degree committee member
|Degree committee member
|Stanford University, School of Engineering
|Stanford University, Department of Bioengineering
|Statement of responsibility
|Submitted to the Department of Bioengineering.
|Thesis Ph.D. Stanford University 2023.
- © 2023 by Yuhang Fan
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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