H2020Индивидуална стипендия2020–2021

IDENSTEM · Identification and characterization of enteric nervous system stem cells

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

Период: 2020-01-01 → 2021-12-31
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Нервните стволови клетки в червата се изследват, за да се разбере как се възстановяват тези тъкани след увреждане. Това помага за разбирането на развитието на храносмилателната система и на заболявания като болестта на Хиршспрунг.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Identification and characterization of enteric nervous system stem cells

Why is important for society? The enteric nervous system (ENS) represents the largest collection of neurons and glial cells outside the central nervous system (CNS) which are intrinsic to the gastrointestinal tract and are essential for digestive function. The ENS controls virtually every aspect of gastrointestinal physiology including intestinal motility, epithelial secretion, and blood flow, while recent evidence indicates that enteric neurons and glia contribute to intestinal epithelial barrier functions and immune homeostasis. Not surprisingly, ENS activity also impacts the dynamics and composition of the complex consortia of microorganisms that colonise the gut shortly after birth. While the ENS regulates gastrointestinal physiology independently of CNS input, it is likely to serve as a relay station along the bidirectional gut-brain axis communication pathways. The critical contributions of the ENS to gastrointestinal physiology and homeostasis are highlighted by life-threatening developmental disorders, such as Hirschsprung disease, characterised by failure of development of enteric ganglia in the distal colon. What is the problem? The identity and properties of ENS neural stem cells (ENSCs) remain undefined and the cellular and molecular mechanisms that maintain ENS homeostasis in the face of adverse environmental influences or repair its neural circuitry following injury or disease, are unknown. We postulate that in vertebrates the EGC compartment exhibits NSC activity and aim to describe its cellular basis and regulation. Preliminary data suggest that a subpopulation of enteric glial cells expressing the Notch signaling target Hes5, undergo low rate proliferation and exhibit neurogenic potential. What are the overall objectives? Here, we aim to identify and characterize the cellular and molecular properties of the ENSSCs and to understand their contribution in maintaining ENS integrity under normal conditions or in response to injury.

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

Цел на проекта

The digestive system is essential for water and nutrient uptake, waste removal and serves as a sensory system providing information to the central nervous system via the gut-brain communication axis. The gastrointestinal tract harbours the largest collection of neurons and glial cells collectively known as the enteric nervous system (ENS) and regulate digestive physiology independently of brain input. Intestinal function and homeostasis depend on the integrated and balanced activity of multiple gut tissues,in which, the ENS plays a critical role by actively interacting with the intestinal immune system, the epithelial barrier and microbiota. Developmental deficits or acquired disorders in any of these tissue components can result in debilitating gastrointestinal conditions, such as Hirschsprung disease (congenital megacolon) or inflammatory bowel disease. Despite critical contributions of the ENS to digestive physiology and intestinal homeostasis, very little is known about the cellular mechanisms that underpin its function at steady state conditions or in response to injury. IDENSTEM will address the identity and properties of ENS neural stem cells (ENSCs) using the mouse as an experimental model organism. Preliminary data suggest that a subpopulation of enteric glial cells expressing the Notch signalling target Hes5, undergo low rate proliferation and exhibit neurogenic potential. In this proposal, we aim to identify and characterize the cellular and molecular properties of this population. We wish to understand their contribution in maintaining ENS integrity under normal conditions or in response to injury/disease. These studies will advance fundamental neurogastroenterology and the development of novel therapeutic strategies for various gut disorders. Furthermore, they will provide insight into ENS contributions to the gut tissue circuitry and in intestinal inflammation. IDENSTEM will open a new window of knowledge to improve human health.

Оригинален текст от CORDIS (на английски).

Участници

THE FRANCIS CRICK INSTITUTE LIMITED · LondonКоординаторОбединеното кралство