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ID2 controls differentiation of entero-endocrine cells in mouse small intestine

ABSTRACT: ID2 controls differentiation of entero-endocrine cells in mouse small intestine

PROVIDER: PRJNA739693 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14871836_1.fastq.gz	Fastqsanger.gz
	SRR14871836_2.fastq.gz	Fastqsanger.gz
	SRR14871837_1.fastq.gz	Fastqsanger.gz
	SRR14871837_2.fastq.gz	Fastqsanger.gz
	SRR14871838_1.fastq.gz	Fastqsanger.gz

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ID2 controls differentiation of entero-endocrine cells in mouse small intestine

Project description:Aim: The mammalian gut is the largest endocrine organ. Dozens of hormones secreted by enteroendocrine cells regulate a variety of physiological functions of the gut but also of the pancreas and brain. Here, we examined the role of the helix-loop-helix transcription factor ID2 during the differentiation of intestinal stem cells along the enteroendocrine lineage. Methods: To assess the functions of ID2 in the adult mouse small intestine, we used single-cell RNA sequencing, genetically modified mice, and organoid assays. Results: We found that in the adult intestinal epithelium Id2 is predominantly expressed in enterochromaffin and peptidergic enteroendocrine cells. Consistently, the loss of Id2 leads to the reduction of Chromogranin A-positive enteroendocrine cells. In contrast, the numbers of tuft cells are increased in Id2 mutant small intestine. Moreover, ablation of Id2 elevates the numbers of Serotonin+ enterochromaffin cells and Ghrelin+ X-cells in the posterior part of the small intestine. Finally, Id2 acts downstream of BMP signalling during the differentiation of Glucagon Like Peptide-1+ L-cells and Cholecystokinin+ I-cells towards Neurotensin+PYY+ N-cells. Conclusion: Id2 plays an important role in cell fate decisions in the adult small intestine. Firstly, ID2 suppresses the differentiation of secretory intestinal epithelial progenitors towards tuft cell lineage and thus controls host immune response on commensal and parasitic microbiota. Next, ID2 is essential for establishing a differentiation gradient for enterochromaffin and X-cells along the anterior-posterior axis of the gut. Finally, ID2 is necessary for the differentiation of N-cells thus ensuring a differentiation gradient along the crypt-villi axis.

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Project description:Early diagnosis of tumors of the small intestine is a challenge for clinicians and for radiologists. The detection of tumors of the small intestine is a field in which the video capsule endoscopy has the lowest performance. The entero-CT with enteroclysis is the imaging technique used primarily to explore patients with a strong suspicion of small intestine tumors. However the entero-CT with enteroclysis has disadvantages : it is irradiating, the nasojejunal tube implies a discomfort to the patient and it is a complicated examination in terms of logistics with necessity of specific equipment to insert the nasojejunal tube. MRI has been proposed as an alternative imaging technique and satisfactory results have been reported with the MRI enteroclysis. However, this technique has several disadvantages related to nasojejunal tube insertion and the necessity of equipment compatible with the high magnetic fields. The enterography-MRI without enteroclysis, whose principle is to distend the small intestine by ingestion of large quantities of a liquid, has a major and undisputed role in the exploration of Crohn’s disease of the small bowel. However, its capacity for distension of the small intestine for optimal tumor detection is questioned and its role in tumor detection is largely unknown.

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