H2020Индивидуална стипендия2020–2022

HUMANE · Transcriptional characterization of human postnatal and adult neural progenitors and of the stem cell niches.

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

Период: 2020-08-01 → 2022-07-31
Финансиране от ЕС: 203 852 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Невронните стволови клетки в човешкия хипокампус и стриатум се анализират чрез секвениране на РНК, за да се установи дали се създават нови неврони при възрастни. Това помага да се разбере как мозъкът се регенерира и как се формира паметта.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Transcriptional characterization of human postnatal and adult neural progenitors and of the stem cell niches.

The discovery of adult neurogenesis in mammals changed the long-lasting view of the brain as an immutable structure and raised new hope for brain regeneration. In the past fifty years adult neurogenesis was found in almost all mammals and has been extensively studied in rodents. Adult born neurons have special properties that significantly influence the activity of the networks into which they integrate, playing important roles in memory formation and cognitive flexibility. Furthermore, adult neurogenesis was shown to regulate affective state and to play a role in depression. Despite the vast body of knowledge regarding rodent adult neurogenesis, the data describing it in humans is scarce. Most studies investigating human adult neurogenesis rely on immunohistology, using biomarkers established in rodents. In this study we set out to test the existence of human adult neurogenesis in an unbiased manner by analysing the transcriptome of the cells present in the hippocampus using single nucleus RNA sequencing. One of the main goals of this project was to identify individual neural progenitors in the human brain and to characterize their transcriptome. We also aimed to characterize in detail the stem cell niches using spatial transcriptomics. The Frisén laboratory showed with the help of 14C-birthdating that adult born neurons are integrating not only in the human hippocampus but also in the striatum. However, it is not known where these neurons are originating from and in which striatal structures they are integrating. Thus, we also aim to analyze the human nucleus accumbens, nucleus caudatus and the putamen and to determine if newly generated neurons are present in these structures. Our project aimed to bring a detailed characterization of human neurogenesis, answering important outstanding questions in the field, and to create protocols and datasets that will be the starting points for numerous future studies investigating human adult neurogenesis in physiological and pathological contexts.

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

Цел на проекта

The presence of adult neurogenesis in humans spurs hope for brain regeneration and changed the view of the brain as an immutable structure. Adult neurogenesis was found in almost all mammals and was extensively studied in rodents. In spite of the vast knowledge accumulated in the field, data describing human adult neurogenesis is controversial. Several studies found neural progenitors in the human brain. Conclusive data was brought by the Frisén group via 14C birthdating, which showed ongoing neurogenesis in the hippocampus and striatum. Other studies based mostly on immunohistological methods and rodent neurogenesis markers, failed to identify neural progenitors in the adult human hippocampus and even questioned the existence of a stem cell niche. These conflicting reports are a clear indication that we need unbiased descriptive studies of human adult neurogenesis. The recent advances in sequencing technologies allow an in-depth transcriptome characterization at a cellular level, making possible an unbiased identification of neural progenitors and of neurogenic niches. The aim of this project is to show beyond doubt whether neural progenitors and stem cell niches are present in the adult human brain using unbiased, state-of-the-art sequencing methods. Furthermore, for the first time we will characterize the transcriptome of single postnatal and adult neurogenic progenitors and of the potential stem cell niches. Our study will not only show whether adult neurogenesis takes place in humans but will also generate tools that will lay the foundation for future studies, boosting the research in the field. Rodent studies showed that adult neurogenesis contributes to brain plasticity, cognitive flexibility and can constitute a future start for regenerative therapies. Thus, our results could open the road for using neurogenesis to fight against neurological disorders especially visible in the aging European society such as age related cognitive decline or depression.

Оригинален текст от CORDIS (на английски).

Участници

KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция