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UK funding (368 954 £) : CONVERSION DE LIGNÉE DE CELLULES PROGÉNITRICES ENDOTHÉLIALES DÉRIVÉES DU SANG EN UN PHÉNOYPE CORTICOSURRÉNALIEN : UNE NOUVELLE TECHNOLOGIE POUR ÉTUDIER LA GLANDE SURRÉNALE. Ukri01/03/2014 UK Research and Innovation, Royaume Uni
Vue d’ensemble
Texte
CONVERSION DE LIGNÉE DE CELLULES PROGÉNITRICES ENDOTHÉLIALES DÉRIVÉES DU SANG EN UN PHÉNOYPE CORTICOSURRÉNALIEN : UNE NOUVELLE TECHNOLOGIE POUR ÉTUDIER LA GLANDE SURRÉNALE.
| Abstract | The adrenal glands are part of the endocrine system, which releases hormones into the blood system. Each adrenal gland is anatomically and functionally composed of two distinct parts, an outer cortex and inner medulla. The adrenal cortex is essential for life: it produces glucocorticoids that regulate body metabolism, and mineralocorticoids that affect blood pressure. Adrenal cortex disorders can cause your adrenal glands to produce too much or not enough hormones; some disorders can be determined by genetic mutations. Adrenal studies are usually carried out by using cell lines established from tumors or cell lines transfected with a gene of interest: both systems have several drawbacks such as the inability to produce a full steroid profile or the inherent difficulty to extrapolate physiologically relevant data from an over-expression system. Animal models are also frequently used to investigate the development, function and pathology of adrenal glands, as well as for testing new treatments and for toxicology studies. However some animal models obtained through knockout technology fail to generate the human disease (Triple-A syndrome and NNT dependent-Familial Glucocorticoid Deficiency are two examples in the adrenal field). Cell reprogramming techniques are becoming powerful tools for replacing animal models and procedures as well as for studying the cause of a particular disease and for drug testing. Cellular reprogramming describes the process where a fully differentiated, specialized cell type is induced to transform into a different cell type that it would not otherwise become under normal physiological conditions. Cellular reprogramming has been achieved using a variety of methods, including somatic cell nuclear transfer, cell-cell fusion and, most recently, through the introduction of transcription factors. Two scientists, Sir John Gordon of Britain and Shinya Yamanaka of Japan were awarded the Nobel Prize for the category Physiology and Medicine in 2012 for their groundbreaking discoveries in the field. Gordon's research was conducted in 1962 and showed that it was possible to reverse the specialization of cells. By transferring a nucleus from a frog's intestinal cell into a frog's egg cell that had its nucleus removed, he was able to obtain a tadpole. Building on Gordon's work, Yamanaka published a paper in 2006 demonstrating that mature murine cells can become immature stem cells (called inducible pluripotent stem cells, IPSCs) by expressing genes encoding four transcription factors. IPSCs can be differentiated to several tissues using specific protocols. Yamanaka's breakthrough opened the door to studying disease and developing diagnosis and treatments. Recently, the generation of a cell type from an unrelated cell type without the need of an IPSCs intermediate has been described by using specific cell fate-transcription factors. This process has been named lineage conversion. Regardless of the method used, skin fibroblasts have been a predominant source material so far but an invasive surgical procedure (skin biopsy) is required to establish primary cells, and not always possible. A blood draw would be an ideal starting point to obtain donor-specific cells because it is minimally invasive and established procedures are already in place for acquisition and handling. In fact, scientists have recently employed this patient-friendly way to establish long-term in vitro culture of blood-derived cells, and importantly, they have been able to reprogram efficiently these cells into IPSCs. One of these cell types are late-outgrowth endothelial progenitor cells (L-EPCs). With this proposal, I aim at developing a technology whereby L-EPCs are reprogrammed to acquire an adrenocortical phenotype using lineage conversion, by forcing the expression of single cell fate regulator, Steroidogenic Factor 1. |
| Category | Research Grant |
| Reference | BB/L002671/1 |
| Status | Closed |
| Funded period start | 01/03/2014 |
| Funded period end | 28/02/2017 |
| Funded value | £368 954,00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FL002671%2F1 |
Participating Organisations
| Queen Mary University of London | |
| QUEEN MARY UNIVERSITY OF LONDON | |
| Technical University of Dresden |
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Queen Mary University of London, Londres, Royaume Uni.
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