Human Pluripotency

Lead Research Organisation: University of Cambridge
Department Name: Wellcome Trust - MRC Cam Stem Cell Inst

Abstract

Pluripotency is the flexible capacity of individual cells to give rise to all somatic lineages. In the human embryo the period of pluripotency extends for more than 10 days, from emergence in the late blastocyst through to lineage commitment during gastrulation. In mice two types of pluripotent stem cell line derived in vitro are thought to represent respectively the initial naïve condition and a late phase primed for differentiation. Human pluripotent stem cells exhibit attributes of priming, reflected in molecular features such as DNA methylation and, most significantly for application purposes, in variable differentiation biases. Recently, however, we have established human stem cell cultures that exhibit properties anticipated for naïve pluripotency. Here we will further validate naïve identity and enhance the stability and consistency of these cultures. We will then characterise their transition towards lineage commitment. Understanding this process and faithfully recapitulating in utero pluripotency progression may substantially improve the robustness and fidelity of directed differentiation for biomedical applications. In vivo reference material is lacking, however, because the peri- and early post-implantation period is essentially inaccessible in human embryo development. Therefore, exploitation of naïve human pluripotent stem cells offers both a unique challenge as well as a substantial opportunity.

The phase of naïve pluripotency in human is only partially conserved with rodents and key factors that support the robust self-renewal of mouse embryonic stem cells are missing. Our first task therefore is to implement both candidate gene studies and genome-wide screens to identify pivotal regulators that can enhance the stability of human naïve pluripotent cells in vitro. We will then optimise the generation of naïve stem cells both by derivation from donated embryos and by reprogramming. In parallel we will establish the conditions for naïve cells to transition to an intermediate, or formative, population that recapitulates the embryonic disk, and subsequently to progress efficiently to lineage specification. We will characterise these conversions by deep transcriptome and epigenome profiling taking advantage on next generation sequencing technology. Having defined the path to lineage specification, we will be positioned to determine the extent to which differentiation biases commonly observed among conventional human pluripotent stem cells may be muted by resetting to naïve pluripotency. Observed restoration of developmental potential will be characterised further to reveal whether "correction" is mediated by transcriptional rewiring and/or epigenome erasure.

Our laboratory possesses the experience and expertise for all the stem cell culture and manipulation aspects of this project. We also have outstanding collaborators in domains of early embryology, CRISPR screening, sequencing informatics, DNA methylome, transposable elements, media formulation, physical biology, computational modelling and genome integrity.

Technical Summary

The goals of the proposed research are: (i) to fully characterise human naïve pluripotency; (ii) to define parameters for robust self-renewal and resetting pluripotency; (iii) to delineate the pathway to multi-lineage specification and commitment. Acquiring the knowledge to harness the naïve form of human pluripotency and thence to reproduce the molecular and cellular ontogeny of pluripotency progression in the embryo should enable more consistent and efficient differentiation behaviour. The concept that differentiation biases observed among conventional human pluripotent stem cells may be muted by transition through naïve pluripotency will then be examined.

The specific research objectives and tasks are:

I. Regulatory network of the human naïve state
i. Examination of core pluripotency regulators
ii. Differential transcriptome analysis
iii. Functional genetic screens
iv. Validation and characterisation of lead candidates
v. Modelling human naïve gene regulatory circuitry

II. Culture optimisation and transgene free resetting
i. Improvement to naïve PSC culture
ii. Global characterisation of consistent identity
iii. Homogeneity of self-renewal
iv. Transgene-free resetting

III. Commitment and differentiation
i. Pathway to multilineage competence
ii. Consistent multilineage differentiation
iii. Restoration of balanced differentiation

The study is focussed on human pluripotent stem cells with associated human embryo studies.
Key methods to be deployed include: genetic engineering of reporters and inducible transgenes; CRISPR/Cas9 based genetic screens; high throughput transcriptome profiling, methylome profiling, ATAC-seq and ChIP seq with associated bioinformatics; human embryo culture and cell line derivation.

Exploitation of the results will be led by the academic research sector but new know-how and intellectual property is also anticipated to foster collaborations and licencing arrangements with service industry and Pharma.

Planned Impact

Stem cell biology is a priority area for UK science investment. The research proposed here is specifically applicable to improving the authenticity, efficiency and reproducibility of directed differentiation of pluripotent stem cells for biomedical goals in drug discovery and regenerative medicine.
Beneficiaries and stakeholders will include:
Academic researchers - this research will contribute to maintaining a world-leading position of the UK in pluripotent stem cell research, as detailed in the Academic Beneficiaries section.
Industry - new insight into culture formulations and protocols for stem cell expansion, differentiation and quality assessment will benefit commercial activities in research tool provision, drug discovery and regenerative medicine. Relevant industry includes reagent companies in the stem cell sector, biotechnology service companies, and Pharma, all of whom are represented in the Cambridge cluster. The project is expected to generate new Intellectual Property, for which we will seek patent protection through the University technology transfer organisation, Cambridge Enterprise. Specialist know-how will be a further basis for collaborative engagement with industry and commercial translation, potentially involving the UK Regenerative Medicine Platform and Cell Therapy Catapult as intermediaries. Industry can also profit from the highly skilled workforce that will be developed over the course of the project. Overall the project will support retention and growth of the Life Sciences industry around Cambridge and in the UK and thereby contribute to economic activity and competitiveness.
Clinicians and patients - ultimately this research is expected to feed through to improved medical care and treatment by enabling more effective exploitation of human pluripotent stem cells. This will include both applications in regenerative medicine and use of reprogrammed cells derived from patients for applications in disease modelling and drug discovery. Knowledge of early human development may also benefit assisted conception by providing additional criteria for assessment of embryo quality.
General public - the project aims to meet expectations for publicly funded research; (i) to increase understanding of the natural world, and (ii) to lead to improved quality of life. In the first domain the research addresses fundamental issues in the biology of human development. For the second, the long-term goal is to enable treatments for debilitating disease through new resources for developing personalised medicine and for implementing cell-based therapy.

Outcomes of the project will be disseminated through a range of communication routes. Seminars, workshops, conference presentations and open access publications will reach relevant academics. The Cambridge Stem Cell Club provides frequent opportunity for informal dialogue and networking with clinical and industry researchers while Cambridge Enterprise and the University Office for Translation provide more formal avenues for identifying and engaging with commercial partners. Austin Smith has personal contacts within management at companies such as StemCell Technologies UK (based in Cambridge), Plasticell and AstraZeneca, and is a member of the Cell Therapy Catapult Scientific Advisory Board.

The Smith laboratory has a track record in public engagement, speaking at schools and science festivals, meeting patient groups, contributing to EuroStemCell, (Europe's Stem Cell Hub http://www.eurostemcell.org/), and hosting work experience projects for sixth form pupils. In 2015 we worked with the Institute Public Engagement Officer to organise a competition for computer game developers on the theme of stem cell fate. The winning game is being taken forward for development into an outreach tool. For the present proposal we aim to design and host two similar types of specific activity, reaching out to different communities.

Publications

10 25 50
 
Description Plasticity of the Pluripotency Network
Amount € 2,499,970 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 01/2020 
End 12/2024
 
Title Human formative pluripotent stem cells. 
Description Formative pluripotent stem cell lines derived from human embryos. Registering with the UK Stem Cell Steering Committee for deposition in the UK Stem Cell Bank. 
Type Of Material Cell line 
Year Produced 2020 
Provided To Others? Yes  
Impact To be determined 
 
Title Human naive epiblast stem cells (HNES cells) 
Description Naive pluripotent stem cell lines derived from human embryos. Registered with the UK Stem Cell Steering Committee for deposition in the UK Stem Cell Bank. 
Type Of Material Cell line 
Year Produced 2016 
Provided To Others? Yes  
Impact To be determined 
 
Description Austin Smith - Microsoft Research 
Organisation Microsoft Research
Country Global 
Sector Private 
PI Contribution CSCI PI: Austin Smith; Computational Modelling.
Collaborator Contribution Collaboration with Stephen Emmott and Sara-Jane Dunn; Computational modelling.
Impact Computational modelling; Joint publications.
Start Year 2013
 
Description Austin Smith - Ramiro Alberio 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Pluripotency in sheep and pig
Collaborator Contribution Pluripotency in sheep and pig
Impact None yet
Start Year 2018
 
Description Austin Smith - StemCell Technologies 
Organisation Stemcell Technologies
Country Canada 
Sector Private 
PI Contribution CSCI PI: Austin Smith; Partner in EC project plus licensing agreement.
Collaborator Contribution Collaboration with Sharon Louis and Allen Eaves; Partner in EC project plus licensing agreement.
Impact Partner in EC project plus licensing agreement.
Start Year 2014
 
Description EuroStemCell 
Organisation Centre for Genomic Regulation (CRG)
Country Spain 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation Dando, Weiss & Colucci Ltd
Country United Kingdom 
Sector Private 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation JDRF Center for Beta Cell Therapy in Diabetes
Country Belgium 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation Life and Brain GmbH
Country Germany 
Sector Private 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation National Institute of Health and Medical Research (INSERM)
Country France 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation University of Galway
Country Ireland 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description EuroStemCell 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Austin is a principal investigator for this collaboration
Collaborator Contribution EuroStemCell, launched in March 2010, unites more than 90 European stem cell and regenerative medicine research labs in a coordinated effort to engage with the public about our science. It is a partnership of scientists, clinicians, ethicists, social scientists and science communicators. It is coordinated by the University of Edinburgh
Impact www.eurostemcell.org
Start Year 2010
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation European Research Centre for Biology and Medicine (Centre Européen de Recherche en Biologie et en Médecine)
Country France 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Leiden University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Pluriomics BV
Country Netherlands 
Sector Private 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Sapienza University of Rome
Country Italy 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Stem Cell Technologies
Country Canada 
Sector Private 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation Technical University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation University College London
Department Division of Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description FP7 Project Pluripotent Stem Cell resources for mesodermal medicine (PluriMes) 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Austin Smith is responsible for overall scientific coordination of the project and leads work package 1, translating current advances and understanding of rodent pluripotency to develop and refine conditions that promote homogeneous naïve state for human pluripotent stem cells.
Collaborator Contribution By interlinking complementary biological and computational expertise, the partners aim to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage.
Impact DOI: http://dx.doi.org/10.1016/j.cell.2014.08.029 DOI:10.1038/nprot.2014.102
Start Year 2014
 
Description Methylation analyses 
Organisation Babraham Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Methylation analyses
Collaborator Contribution Methylation analyses
Impact n/a
Start Year 2011
 
Description PluriMes Consortium 
Organisation Technical University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution Coordinator: A consortium of 12 European partners awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle.
Collaborator Contribution The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge.
Impact PMID: 28765214 PMID 25215486
Start Year 2014
 
Description Pluripotency in marmoset 
Organisation Central Institute for Experimental Animals (CIEA)
Country Japan 
Sector Private 
PI Contribution Pluripotency in marmoset
Collaborator Contribution Pluripotency in marmoset
Impact None yet
Start Year 2019
 
Description Potential of pluripotent stem cells for use in regenerative and transplantation medicine 
Organisation University of Tokyo
Country Japan 
Sector Academic/University 
PI Contribution Potential of pluripotent stem cells for use in regenerative and transplantation medicine
Collaborator Contribution Potential of pluripotent stem cells for use in regenerative and transplantation medicine
Impact Publication: Development 2021 Vol. 148 Issue 23 DOI: 10.1242/dev.199901
Start Year 2019
 
Title Novel marker for naïve pluripotent cells 
Description Novel marker SUSD2 for naïve pluripotent cells. 
IP Reference GB1804618.5 
Protection Patent application published
Year Protection Granted 2018
Licensed Yes
Impact No notable impact.
 
Title PLURIPOTENT STEM CELLS 
Description The invention provides processes for producing or propagating a formative stem (FS) cell line, from one or more precursor pluripotent stem cells, which process comprises: (a) providing a one or more precursor pluripotent stem cells; (b) culturing the precursor pluripotent stem cells in formative stem cell culture media. The formative stem cell culture media comprises limited amounts of activin and exogenous fibroblast growth factor, but includes a Wnt inhibitor, and typically a retinoic acid receptor inhibitor. The invention further provides related materials and methods for use in preparing and utilising FS cell lines. 
IP Reference WO2018138281 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact There is no notable impact.
 
Description BBC Science & Technology 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Commentary for BBC Science & Technology, Jan 2018
Year(s) Of Engagement Activity 2018