H2020Индивидуална стипендия2019–2021

NeuroStemX · In vitro model of Fragile X Syndrome using naïve iPSCs

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

Период: 2019-06-01 → 2021-08-31
Финансиране от ЕС: 183 473 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Генът FMR1 и неговото изключване се проучват чрез създаване на лабораторни модели от стволови клетки на пациенти със синдрома на X-крехкост. Това помага да се разбере кога точно се променя работата на гена по време на развитието на човешкия мозък.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

In vitro model of Fragile X Syndrome using naïve iPSCs

Fragile X Syndrome (FXS) is the leading cause of inherited mental retardation, intellectual disability, and is the single most common cause of autism spectrum disorders. The trinucleotide repeat expansion, methylation and epigenetic silencing of fragile mental retardation 1 (FMR1) gene promoter leads to the loss of the corresponding protein. However, the timing and cell type affected by FMR1 silencing in the brain of FXS patients are still unknown due to the absence of reliable in vivo and in vitro models. The general objective of NeuroStemX project was the investigation of the genetic and epigenetic modifications of FMR1 locus during the ealy embrionic stage of neural development by means of an in vitro innovative patient-specific human model. Human model based on naïve iPSCs (which represent the in vitro counterpart of pre-implantation pluripotent stem cells) has the potential to reproduce the human neural development from an early pluripotency stage to a late neural differentiation in neurons and brain organoids, reproducing in vitro the molecular events that lead to FMR1 silencing in vivo in human FXS embryos. NeuroStemX project addressed some of the most crucial problems related with FXS pathogenesis and modelling using an original approach based on the use of a new innovative technique to derive naïve iPSCs from somatic cells (skin fibroblasts) developed in Prof. Elvassore group and the generation of FXS neurons with various approaches that I learned during my PhD and PostDoc periods, in combination with the micro technologies based on microfluidics mastered in Prof. Elvassore’s team. The NeuroStemX project focused on 2 specific aims: 1) identifying the timing of FMRP silencing during neural development using naïve iPSCs and 2) establishing a reliable in vitro system to model neuronal defects observed in FXS patients. We hypothesize that the investigation of the early phase of human neural development in human model of Fragile X Syndrome (FXS) are fundamental for the establishment of a targeted therapeutic strategy.

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

Цел на проекта

Neurological and mental disorders are top priorities for the European Commission, which actively invests in research aimed at better understanding brain function and dysfunction, and at finding new therapies for brain disorders. Fragile X syndrome (FXS) is the major monogenetic cause for intellectual disability and is frequently associated with autism spectrum disorder. The trinucleotide repeat expansion, methylation and epigenetic silencing of fragile mental retardation 1 (FMR1) gene promoter leads to the loss of the corresponding protein. However, the molecular mechanism and the timing leading to FMR1 silencing are still unknown due to the absence of reliable in vivo and in vitro models. The recent development of naïve PSCs showing a broader unmethylated genome (including in FMR1) opened a new hope for disease modeling of FXS, but data are still partial and contradictory. The NeuroStemX project aims at filling this gap taking advantage of an optimized technique for the generation of naïve iPSCs developed at the University of Padova (UniPd) and generation of FXS neurons with various approaches mastered by the Experienced Researcher (ER) in conjunction with the microtechnologies developed by UniPd. In particular, we aim at 1) identifying the timing of FMRP silencing during neural development using naïve iPSCs and 2) establishing a reliable in vitro system to model neuronal defects observed in FXS patients. In this project, we are addressing some of the most crucial problems related with FXS pathogenesis and modeling using a variety of innovative approaches. This will give the ER an outstanding training-through-research opportunity by means of a personalized multidisciplinary project, in which the ER will enlarge her scientific competences and strengthen her professional profile. The training includes both scientific and transferable skills, aimed at the reinforcement of the ER professional maturity and independence.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA DEGLI STUDI DI PADOVA · PadovaКоординаторИталия