Dissecting adult epithelial cell plasticity using a model of oesophageal-to-skin lineage conversion
type: CreativeWork
description: Epithelial cells possess a remarkable capacity to rapidly adapt their cell fate programme in response to changing tissue demands. Upon tissue injury or environmental perturbations, adult committed cells can reacquire stem cell properties, thereby expanding the pool of cells that contribute to tissue regeneration. Notably, this ability to rewire the cell fate programme – known as cell fate plasticity – extends beyond physiological constraints. When exposed to ectopic cues, epithelial cells can alter their identity as directed by the surrounding microenvironment. A deeper understanding of the mechanisms that govern these changes in cell identity holds great promise for regenerative medicine. However, our current knowledge of these processes is very limited. Here, I adapted an *ex vivo* regenerative model to investigate adult oesophageal cell fate in response to the ectopic microenvironment of the skin. For this, I exposed the appendage-free mouse oesophageal epithelium to the mouse skin dermis, bearing empty niches for hair follicles. Whole-mount techniques together with immunofluorescence analysis revealed that oesophageal cells re-epithelialized the skin dermis and underlying niches, forming a new epithelium with associated appendages structurally similar to hair follicles. By looking into surrogate markers of oesophageal and skin lineages, I found that oesophageal cells were instructed to change towards the skin lineage. Further investigation confirmed that the cues dictating lineage conversion emerged from the skin dermis. Yet, histological characterization and transcriptomic analysis unveiled high heterogeneity in response to dermal signals, denoting the inefficiency of the lineage conversion process. To investigate the mechanisms promoting/preventing oesophageal-to-skin lineage conversion, I made use of an in-depth single cell RNA sequencing dataset. Interestingly, cells transitioning towards skin identity showed a regenerative profile defined by a marked hypoxi…
abstract: Epithelial cells possess a remarkable capacity to rapidly adapt their cell fate programme in response to changing tissue demands. Upon tissue injury or environmental perturbations, adult committed cells can reacquire stem cell properties, thereby expanding the pool of cells that contribute to tissue regeneration. Notably, this ability to rewire the cell fate programme – known as cell fate plasticity – extends beyond physiological constraints. When exposed to ectopic cues, epithelial cells can alter their identity as directed by the surrounding microenvironment. A deeper understanding of the mechanisms that govern these changes in cell identity holds great promise for regenerative medicine. However, our current knowledge of these processes is very limited. Here, I adapted an *ex vivo* regenerative model to investigate adult oesophageal cell fate in response to the ectopic microenvironment of the skin. For this, I exposed the appendage-free mouse oesophageal epithelium to the mouse skin dermis, bearing empty niches for hair follicles. Whole-mount techniques together with immunofluorescence analysis revealed that oesophageal cells re-epithelialized the skin dermis and underlying niches, forming a new epithelium with associated appendages structurally similar to hair follicles. By looking into surrogate markers of oesophageal and skin lineages, I found that oesophageal cells were instructed to change towards the skin lineage. Further investigation confirmed that the cues dictating lineage conversion emerged from the skin dermis. Yet, histological characterization and transcriptomic analysis unveiled high heterogeneity in response to dermal signals, denoting the inefficiency of the lineage conversion process. To investigate the mechanisms promoting/preventing oesophageal-to-skin lineage conversion, I made use of an in-depth single cell RNA sequencing dataset. Interestingly, cells transitioning towards skin identity showed a regenerative profile defined by a marked hypoxi…
author: Jimenez Gomez, Paula
language: eng
keywords: Cell fate, Epithelial, HIF1a, Plasticity, Regeneration, SOX9, Stem Cells
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/abc15163-91f3-4668-b04f-4771168cd28d/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-06-01
date modified: 2026-07-22T22:24:10Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.99741