H2020Индивидуална стипендия2016–2017

TOTIPOTENCY2014 · Dissecting the epigenetic control of totipotency.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-01-01 → 2017-12-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Генната регулация при ранното развитие на ембриони от мишки показва как една клетка се превръща в различни видове тъкани. Разбирането на този процес помага за подобряване на препрограмирането на възрастни клетки, което е важно за регенеративната медицина и замяната на органи.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Dissecting the epigenetic control of totipotency.

Mammalian development is a remarkable process. Following fertilisation of the egg by the sperm, the embryo must grow from a single cell capable of generating every cell type, to a group of cells each with their own identity. This requires tight regulation and control, which is carried out by factors that turn the correct genes on and off at the right developmental stage. However, due to the small number of cells, technical and ethical limitations, it has been traditionally extremely difficult to study this important developmental time. Using the mouse as a model, this project uses exciting cutting-edge technologies to investigate how genes are regulated through early development. It explores the similarities and differences between single cells within and between embryos, and how these are regulated. Additionally, these findings will be applied to a new technology termed ‘reprogramming’, which induces adult cells into a different cell type, for example turning a skin cell into a liver cell. The future medical promise of this technology for regenerative medicine and organ replacement is enormous. However before its clinical use becomes reality, it must be better understood and its pitfalls amended, which this project aims to help achieve. The work plan consists of four specific objectives: 1. Characterisation and validation of early-embryonic like (EEL) cells as a model of totipotency. 2. Identification of EEL regulators through a novel candidate-based screen. 3. Mechanistic studies on selected EEL regulators, including 2 preliminary candidates. 4. Assessing the role of EEL regulators in the efficiency and fidelity of somatic reprogramming.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

One of the most critical epigenetic and chromatin remodelling processes in mammalian development occurs shortly after fertilization restoring totipotency. Due to limited cell numbers and lack of experimentally tractable systems, the mechanisms and regulation of this developmental stage are poorly understood. This proposal will provide important mechanistic insights into the epigenetic control of early embryonic gene expression, and its relevance to somatic reprogramming. Murine embryonic stem cells (ESCs) contain a rare sub-population of early embryonic like (EEL) cells expressing genes normally restricted to the pre-implantation embryo, with enhanced extra-embryonic differentiation capability. Firstly, using novel single-cell technologies, I will characterize the EEL cells in detail, validating them as an in vitro model of pre-implantation development. On-going research in the host lab that I am involved in has identified an epigenetic enhancer that expands this EEL sub-population. Through bioinformatic analysis of pre-implantation transcriptome data, I have shortlisted 34 epigenetic and chromatin-associated proteins, including the previously identified factor, which will be systematically screened to identify new enhancers of totipotency. Validated EEL regulators, including two additional newly confirmed factors, will be analysed mechanistically determining their interaction partners, interdependencies, and mode of action. Finally, the contribution of the totipotency regulators towards the efficiency and fidelity of somatic reprogramming will be determined, potentially improving the use of this technology for personalised gene therapy and regenerative medicine.This state-of-the-art proposal uses innovative and novel cutting-edge technologies and combines the expertise of the researcher and the host. It has the potential for significant impact across several fields from epigenetics and stem cell biology to reprogramming and regenerative medicine.

Оригинален текст от CORDIS (на английски).

Участници

THE BABRAHAM INSTITUTE · CambridgeКоординаторОбединеното кралство