H2020Индивидуална стипендия2022–2024

Neuro-ReprOmics · Deconstructing in vivo glia-to-neuron conversion

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

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Глиалните клетки в мозъка се анализират, за да се разбере как могат да бъдат превърнати в неврони чрез специфични протеини. Това помага за разработването на методи за замяна на увредени неврони при невродегенеративни заболявания и подобряване на мозъчната регенерация.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Deconstructing in vivo glia-to-neuron conversion

The project addresses the challenge of understanding and influencing neuronal reprogramming in the brain, specifically focusing on how certain transcription factors can drive cellular transitions to neuronal states. This research involves examining gene expression, chromatin accessibility, and cellular phenotypes post-reprogramming, aiming to decode key molecular mechanisms. By leveraging advanced multiomic techniques such as single-cell RNA sequencing, ATAC sequencing, and spatial transcriptomics, the project seeks to uncover the intricate regulatory networks involved in neuronal reprogramming. This work is of immense importance for society, particularly in the context of neurodegenerative diseases. The ability to reprogram cells into functional neurons offers transformative therapeutic potential, paving the way for innovative treatments aimed at replacing damaged or lost neurons. Additionally, understanding the molecular processes behind neuronal reprogramming could lead to breakthroughs in neuroplasticity and brain regeneration, providing insights into strategies for cognitive health preservation and recovery. The overall objectives of the project include profiling gene expression and chromatin states across various reprogramming stages, establishing robust methodologies for combined single-cell RNA sequencing, ATAC sequencing, and spatial transcriptomics, and developing experimental techniques for in vivo tracking and analysis of reprogrammed cells at different stages. These objectives aim to contribute to a detailed understanding of cell fate transitions in the central nervous system and the role of transcription factors in neuronal development and plasticity.

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

Цел на проекта

Direct lineage reprogramming of cell identity in the nervous system offers the prospect of remodelling diseased brain circuits. Recent years have provided evidence for the possibility of converting brain glia into neurons in vivo. This may eventually allow to regenerate neurons that have degenerated as a consequence of injury or disease. Yet, the process by which glial cells give up their original identity and adopt a neuronal fate remains by large enigmatic. Moreover, the knowledge of molecular underpinnings of glia-to-neuron conversion is lacunary and virtually nothing is known about the process in vivo. The Berninger laboratory has discovered specific cocktails of reprogramming factors that gives rise to induced neurons in the mouse cerebral cortex, with some cells adopting hallmark features of fast-spiking, parvalbumin-expressing interneurons, a neuronal subtype that is highly vulnerable in neuropsychiatric and neurological disorders. The aim of my project addresses the question of how these neurogenic reprogramming factors remodel gene expression programs as glial cells convert into neurons. Thus, I will utilize defined combinations of reprogramming factors leading to the generation the distinct types of neurons to elucidate how and when the reprogramming trajectories diverge. Towards this end, I will establish single cell RNA sequencing as well as scATAC-seq from cells undergoing conversion in vivo to uncover the transcriptomic and epigenomic changes that drive this process. The outcome of this study is twofold, as this will break new ground in our understanding of how transcription factors can overcome existing cell-specific gene expression programs to induce new cellular identities, and at the same time identify new molecular handles for rendering reprogrammed cells more similar to their endogenous counterparts in an attempt to improve the prospects of using this strategy for brain repair.

Оригинален текст от CORDIS (на английски).

Участници

KING'S COLLEGE LONDON · LondonКоординаторОбединеното кралство