A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids
Abstract/Contents
- Abstract
- Organoids are powerful experimental models for studying the ontogeny and progression of various diseases including cancer. Organoids are conventionally cultured in bulk using an extracellular matrix mimic. However, organoids cultured in bulk physically overlap, making it impossible to track the growth of individual organoids over time in high throughput. Moreover, local spatial variations in bulk matrix properties make it difficult to assess whether observed phenotypic heterogeneity between organoids results from intrinsic cell differences or differences in microenvironment. Here, we developed a microwell-based method that enables high-throughput quantification of image-based parameters for organoids grown from single cells, which can further be retrieved from their microwells for sequencing and molecular profiling. Coupled with a deep-learning image processing pipeline, we characterized phenotypic traits including growth rates, cellular movement, and apical-basal polarity in two CRISPR-engineered human gastric organoid models, identifying genomic changes associated with increased growth rate and changes in accessibility and expression correlated with apical-basal polarity.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Sockell, Alexandra Frances Adams |
|---|---|
| Degree supervisor | Curtis, Christina |
| Degree supervisor | Fordyce, Polly |
| Thesis advisor | Curtis, Christina |
| Thesis advisor | Fordyce, Polly |
| Thesis advisor | Sherlock, Gavin |
| Thesis advisor | Steinmetz, Lars |
| Degree committee member | Sherlock, Gavin |
| Degree committee member | Steinmetz, Lars |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Alexandra Sockell. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/nq241rd1170 |
Access conditions
- Copyright
- © 2023 by Alexandra Frances Adams Sockell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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