H2020Индивидуална стипендия2016–2018

CACOHET · “Causes and consequences of pluripotency gene regulatory network member heterogeneity”

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

Период: 2016-08-01 → 2018-07-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Плурипотентните стволови клетки и начинът, по който протеини като Nanog регулират тяхното самовъзпроизвеждане или превръщане в други тъкани, са в центъра на анализа. Разбирането на тези механизми помага за развитието на регенеративната медицина и терапии, базирани на клетки.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

“Causes and consequences of pluripotency gene regulatory network member heterogeneity”

Pluripotent stem cells harbor great potential when it comes to disease modelling, regenerative medicine and future cell-based therapies, as they can self-renew and differentiate in virtually all cell types of the human body. To fully exploit the potential of these cells, a thorough understanding of the mechanisms regulating this pluripotent cell state is required. How stem cell populations balance the opposing forces of self-renewal and differentiation to maintain a functional population is a question that strikes at the heart of what it means to be a stem cell. Undifferentiated embryonic stem cell (ESC) identity is maintained by transcription factors (TFs) of the pluripotency gene regulatory network (PGRN) centred on the TFs Oct4, Sox2 and Nanog. ESCs with high levels of Nanog self-renew efficiently while ESCs with low Nanog levels are prone to differentiate. Therefore, the observed heterogeneous expression of some PGRN components, in particular Nanog, is likely to be important for simultaneous maintenance of self-renewal and facilitation of differentiation, thereby sustaining functional pluripotency. Despite the fact that in the last decade considerable progress in our understanding of the regulatory mechanisms underlying pluripotency has been achieved, it is still rather unclear how the PGRN signals down to the DNA sequences and how this affects the gene expression of genes crucial for maintaining the pluripotent state.

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

Цел на проекта

How stem cell populations balance the opposing forces of self-renewal and differentiation to maintain a functional population is a question that strikes at the heart of what it means to be a stem cell. Undifferentiated embryonic stem cell (ESC) identity is maintained by transcription factors (TFs) of the pluripotency gene regulatory network (PGRN) centred on the TFs Oct4, Sox2 and Nanog. ESCs with high levels of Nanog self-renew efficiently while ESCs with low Nanog levels are prone to differentiate. Therefore, the observed heterogeneous expression of some PGRN components, in particular Nanog, is likely to be important for simultaneous maintenance of self-renewal and facilitation of differentiation, thereby sustaining functional pluripotency. In this proposal I will unravel mechanisms establishing heterogeneity and characterise the role of Nanog in generating ESC heterogeneity. By determining chromatin binding dependencies between TFs and by using a novel approach to identify functional cis-elements that mediate Nanog action, these studies will illuminate mechanisms regulating ESC phenotype. The hypothesis that pluripotency is generated by heterogeneity in PGRN component expression, that then generates an ESC population in which single cells have distinct intrinsic probabilities for differentiation into specific cell types will be tested. Interfering with PGRN component function locus-specifically using a high efficiency genome engineering strategy, will explore a new method to influence cell-fate. Together, the proposed innovative experiments aim to increase the understanding of the causes and consequences of PGRN component heterogeneity and the regulation of pluripotency that may be of relevance to other stem cell systems. The results will have important implications for ESC biology, in terms of increasing the efficiencies of ESC derivation, differentiation, and the use of ESCs in future cell based regenerative medicine approaches.

Оригинален текст от CORDIS (на английски).

Участници

THE UNIVERSITY OF EDINBURGH · EdinburghКоординаторОбединеното кралство