In vivo mapping of neural genes in neuroendocrine, neuronal, and glial cells during embryonic lung development
Abstract/Contents
- Abstract
- Small-cell lung cancer (SCLC) is the most deadly form of lung cancer. The disease primarily arises from pulmonary neuroendocrine cells (PNECs), a specialized epithelial cell subtype with numerous sensory and regulatory functions. During development, PNEC progenitors undergo slithering, a unique form of directed migration. Reactivation of slithering in adulthood may explain how normal PNECs transform into tumor cells. Currently, the molecular basis of slithering is unclear. Furthermore, expression of the earliest known PNEC marker, Ascl1, is not exclusive to the cell class during embryonic development. The timing and pattern of Ascl1 expression in these non-PNEC lineages have not been well characterized. Furthermore, subtypes of SCLC may arise from or be influenced by these non-PNEC Ascl1+ cells. Using an inducible-Cre mouse model, this study finds two distinct waves of Ascl1 expression in pulmonary development. Neuronal and glial cell precursors exhibit the first, transient wave; PNEC progenitors exhibit the second wave and sustain Ascl1 expression into adulthood. The same model was used to evaluate the slithering candidacy of several proneural genes identified via in silico analysis of single-cell RNA sequencing (scRNA-seq), with results verified by RNA hybridization and/or immunostaining. The proneural transcription factor Myt1 appears more consistent with a post-slithering role, as well as roundabout receptors Robo1,2 canonically known for their involvement in axon migration. scRNA-seq analysis also detected expression of the actin bundler Fscn1 in PNEC progenitors along with cells of the pulmonary stroma. These results provide the beginnings of a temporal framework for neuroendocrine, neuronal, and glial development that may aid in mapping expression timelines for other predicted lineage markers. More broadly, it is a first step towards understanding the signal pathways that underlie slithering, which may provide insight into developing targeted therapies for SCLC and other pulmonary diseases of neuroendocrine origin.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | May 1, 2022 |
Creators/Contributors
| Author | Tan, Mingqian |
|---|---|
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Kuo, Christin |
| Thesis advisor | Red-Horse, Kristy |
Subjects
| Subject | Biology |
|---|---|
| Subject | Pulmonary |
| Subject | Neuroendocrine |
| Subject | Slithering |
| Subject | Ascl1 |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred citation
Tan, Mingqian; Kuo, Christin; and Red-Horse, Kristy. (2021). In vivo mapping of neural genes in neuroendocrine, neuronal, and glial cells
during embryonic lung development. Stanford Digital Repository. Available at: https://purl.stanford.edu/dz307rz0110
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- mtan8@stanford.edu
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