H2020Индивидуална стипендия2021–2023

GUTMAPS · Cellular cartography of the intestine in health and inflammation

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

Период: 2021-05-01 → 2023-04-30
Финансиране от ЕС: 187 572 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Клетъчната архитектура на червата при здрави хора и пациенти с възпалителни заболявания се анализира чрез разположението на различните видове клетки. Това помага за разработването на нови лекарства и терапии за хора, които не реагират на сегашните методи за лечение.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Cellular cartography of the intestine in health and inflammation

Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major forms of inflammatory bowel disease (IBD). They affect an estimated 4 million people in the United States and Europe and have a rising incidence in the developing world. Both conditions are incurable, often diagnosed at a young age and are associated with significant morbidity and socio-economic costs. Considerable progress in understanding the pathogenesis of IBD has been achieved within the last decade, with notable advances in the contribution of genetic susceptibility, epithelial barrier dysfunction, microbial flora and environmental factors. Currently, around 40% of patients fail to respond to or lose response to currently available immunotherapies. To make progress in developing novel drugs and therapies to treat IBD, it is crucial to first understand the composition and architecture of the intestine in greater detail. Considerable progress has been made in understanding the composition of this organ with the advent of recent single cell RNA sequencing (scRNA-seq) technologies. Although scRNA-seq is a very powerful technique, important spatial information is lost as soon as tissues are dissociated. So even if we now know more about the composition of the intestine, we still lack considerable information about its architecture, especially the localisation of various cell types and niches within it. A recent study from the lamina propria of CD patients using scRNA-seq and multiplexed imaging, identified a unique cellular signature (comprising of immune and stromal cells) associated with resistance to anti-TNF therapy. Patients presenting with this signature/module showed a unique cellular organisation in their inflamed tissues as compared to patients who did not present this module. Such data confirm that understanding the cellular architecture of any organ is as important as understanding its composition. This knowledge is currently lacking and thus the objective of this this MSC action, “ Cellular Cartography of the intestine in health and inflammation” was to map the architecture of the intestine in health and inflammation.

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

Цел на проекта

The intestinal epithelium is the first line of defence of the mucosal immune system because it acts as a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. This barrier is mainly formed by a monolayer of specialised intestinal epithelial cells (IECs) that are crucial in maintaining intestinal homeostasis. Damage to this epithelial layer can increase intestinal permeability and lead to abnormalities in interactions between IECs, stromal cells and immune cells in the underlying lamina propria thereby disturbing the intestinal immune homeostasis, all of which are a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major forms of IBD, affecting an estimated 4 million people in the United States and Europe and have a rising incidence in the developing world. Recent single cell RNA seq (scRNAseq) studies of the intestine have allowed us to understand this organ in unprecedented detail, however, such studies still require the dissociation of tissue and loss of spatial resolution. With this project, I would like to take advantage of recent advances in in-situ sequencing to study intestinal tissue in toto and by combining this with the available scRNA-seq data, generate spatial maps of the intestine (GUTMAPS). The results obtained here will allow us to look at tissue composition and cell-cell interactions with unprecedented resolution in normal and diseased mucosa.

Оригинален текст от CORDIS (на английски).

Участници

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM · RotterdamКоординаторНидерландия