H2020Индивидуална стипендия2020–2022

EmbryoPAINT · PAINTing the architecture of the totipotency gene network during early mammalian development

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

Период: 2020-09-01 → 2022-08-31
Финансиране от ЕС: 162 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Структурата на ДНК в ранните ембриони на мишки се анализира на нанониво, за да се проследи кои гени се активират при първото разделяне на клетките. Това помага да се разбере как една оплодена яйцеклетка се превръща в сложен организъм с различни видове 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

PAINTing the architecture of the totipotency gene network during early mammalian development

While the different cell types found in the human body have very different morphologies and functions, each cell has an identical set of chromosomes with the same genetic sequence and is derived from only a single fertilised egg cell. Therefore, to give rise to different cell types, DNA activity is regulated at the level of its physical structure and by chemical modifications throughout mammalian development. These changes are responsible for the activation or the silencing of different sets of genes and thus for the differentiation of the early embryo into an intricate organism with many different cell types. In order to study the relationship between these structural changes of DNA and the first cell fate decisions during mammalian development, this project aimed at i) developing a technology that would allow us to interrogate DNA structure at the nanoscale in whole preimplantation mouse embryos and ii) use this technology to gain insights into the structural changes occurring at a set of marker genes which are activated during the first cellular differentiation step in early embryogenesis.

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

Цел на проекта

The three-dimensional architecture of the genome regulates its fundamental functions such as the transcription or replication of DNA. Thus, chromatin organisation is crucially important for key aspects of cell biology, such as the differentiation of stem cells in the early embryo. While recent studies have shown that the mammalian genome rearranges extensively towards a more ordered state after the first few embryonal divisions, many fundamental questions remain unanswered. For example, it is not known whether totipotent cells have a well-defined genomic architecture or whether this architecture is highly heterogeneous between different cells and embryos. Further, it is unclear if early cell fate decisions are driven by a reproducible coordinated rearrangement of pluripotency-related genes, or if this is stochastic process. These questions could best be tackled by directly assessing the physical genome structure and architecture of pluripotency genes in single stem cells inside the whole embryo. In my project, I will pursue this ambitious aim by exploiting recent breakthroughs in 3D super-resolution microscopy, namely the development of an inverted lattice light-sheet microscope, highly multiplexed oligo-DNA-PAINT, and advanced computational algorithms, to study the physical 3D architecture of the genomic network of totipotency and pluripotency genes. Thus, I will for the first time be able to unravel the structural determinants of the transition from totipotency to the pluripotent and differentiated state during early mammalian development.

Оригинален текст от CORDIS (на английски).

Участници

EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergКоординаторГермания