Development of pluripotent cell lines from Livestock, and animal models for pharmacology/toxicology applications

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

Reprogramming of cells to a pluripotent embryonic state through iPSC (induced pluripotent stem cell) based technologies has revolutionised prospects for the development of cellular therapies and drug development. Successful translation of these advances to animal research models and livestock has important applications in developing cell-based experimental platforms for studying the genetic and molecular basis of the healthy organism, production traits and disease resistance -
as well as disease progression, intervention strategies, drug testing and toxicology. Unfortunately, until now reprogramming strategies for non-murine or human cells has met with limited success. However, very recent advances in understanding the requirements for reprogramming and the development of culture systems that promote the expansion of extended pluripotent stem cells have meant that generating and exploiting reprogrammed animal cells is now possible1-3. The overall aim of this project is to develop reprogrammed animal cells using these contemporary state-of-the-art methodologies, characterise their differentiation potential and investigate their utility. Initially the project will focus on novel iPSCs provided by Professor Pentao Liu at the Sanger Institute. These cells have been created using these novel technologies and have been made available for the project.
The objectives of the project are:
1. Evaluate the self-renewal properties of the extended pluripotent stem cells and translate this technology to the derivation of iPSCs from other species - including animals used in pharmacology/toxicology applications. This will test the hypothesis that these novel technologies are more effective for reprogramming and promoting propagation of stem cells from different species and contribute to understanding the regulation of cellular signalling mechanisms within these cells.
2. Evaluate the differentiation potential of these novel pluripotent cells and determine if this can be manipulated through genetically modification. This will test the hypothesis that loss and gain of function experiments can direct the programming and expansion of specific progenitor cells from these novel cell lines. This will involve the use of CRISPR gene editing to generate lineage marked cells (e.g. muscle, gut, macrophage) to monitor differentiation.
This project will complement the application of cell based systems for interrogating the wealth of genetic data from animal breeding experiments, as part of the Roslin Institutes new BBSRC Institute Strategic Programme, and will broaden the scope of the iPSC-related expertise at Censo biotechnologies.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/R506151/1 01/10/2017 31/05/2022
1959635 Studentship BB/R506151/1 01/10/2017 30/09/2021 Thomas Watson