The Role of Cervical Reserve Cells in Epithelial Regeneration and Homeostasis in the Murine and Human Cervix
type: CreativeWork
description: How cervical epithelium maintains homeostasis and repair, and how the high-risk human papilloma viruses (HR-HPV) drive neoplasia at the cervical transformation zone (TZ) has been poorly researched. The cervical TZ is thought to be a stem cell niche as it harbours a unique cell population called reserve cells. Reserve cells (marked by KRT17) are believed to have a dual fate ability depending on local microenvironment, in a process of metaplasia (1). However, this belief was based on observational studies. Metaplasia is thought to be the way that the cervical epithelium recovers after an injury (2). Developing an in vitro model that is truly representative of normal cervical epithelium is crucial to address basic questions about homeostasis mechanism and the role of reserve cells in HR-HPV infections. In recent years, advances in modelling the human tissue in 3D manner using organoids have been made (3). In this thesis, a 3D murine cervical organoid model was established. Two distinct microenvironments for the growth of endocervix and ectocervix is defined. Generated cultures retain their proliferative capacity over several months and are representative of the epithelial population in vivo. Furthermore, steps were taken towards optimising human cervix organoids. The established in vitro system was exploited along with in vivo samples to further to uncover specific signalling pathways that regulate the different cervical lineages (endo and ectocervix) using Affymetrix microarray and immunofluorescence techniques. Wnt signalling was found to regulate the endocervical lineage, whilst Notch pathway was active in the ectocervix. Moreover, a novel P75 NGF receptor was found to be expressed in the basal squamous epithelium and in the reserve cells. Additionally, the established organoids were utilised together with lineage tracing techniques to investigate the dual-fate potential of KRT17 cells and their contribution in cervical TZ formation. Two transgenic mice strains were…
abstract: How cervical epithelium maintains homeostasis and repair, and how the high-risk human papilloma viruses (HR-HPV) drive neoplasia at the cervical transformation zone (TZ) has been poorly researched. The cervical TZ is thought to be a stem cell niche as it harbours a unique cell population called reserve cells. Reserve cells (marked by KRT17) are believed to have a dual fate ability depending on local microenvironment, in a process of metaplasia (1). However, this belief was based on observational studies. Metaplasia is thought to be the way that the cervical epithelium recovers after an injury (2). Developing an in vitro model that is truly representative of normal cervical epithelium is crucial to address basic questions about homeostasis mechanism and the role of reserve cells in HR-HPV infections. In recent years, advances in modelling the human tissue in 3D manner using organoids have been made (3). In this thesis, a 3D murine cervical organoid model was established. Two distinct microenvironments for the growth of endocervix and ectocervix is defined. Generated cultures retain their proliferative capacity over several months and are representative of the epithelial population in vivo. Furthermore, steps were taken towards optimising human cervix organoids. The established in vitro system was exploited along with in vivo samples to further to uncover specific signalling pathways that regulate the different cervical lineages (endo and ectocervix) using Affymetrix microarray and immunofluorescence techniques. Wnt signalling was found to regulate the endocervical lineage, whilst Notch pathway was active in the ectocervix. Moreover, a novel P75 NGF receptor was found to be expressed in the basal squamous epithelium and in the reserve cells. Additionally, the established organoids were utilised together with lineage tracing techniques to investigate the dual-fate potential of KRT17 cells and their contribution in cervical TZ formation. Two transgenic mice strains were…
author: Alzamil, Lama
language: eng
keywords: Organoids, cervix, metaplasia
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c546659a-5dd7-4f7f-8bc8-5426f76404ce/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-01-01
date modified: 2026-07-22T22:24:08Z
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.75317