enhanced-spatial-mapping-mouse-gastric-muscle-layers-using-modified

Enhanced Spatial Mapping of Mouse Gastric Muscle Layers Using a Modified Swiss Roll Technique

Spatial "omics" technologies provide unprecedented opportunities to study the biology and interactions of individual cells of the gastric neuromuscular ...

Mayo Clinic College of Medicine and Science

Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging.

Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation.

Neurointestinal diseases result from dysregulated interactions between the nervous system and the gastrointestinal (GI) tract, leading to conditions such as Hirschsprung's disease and irritable bowel syndrome. These disorders affect many people, significantly diminishing their quality of life and overall health. Central to GI motility are the interstitial cells of Cajal (ICC), which play a key role in muscle contractions and neuromuscular transmission. This review highlights the role of ICC in neurointestinal diseases, revealing their association with various GI ailments. Understanding the functions of the ICC could lead to innovative perspectives on the modulation of GI motility and introduce new therapeutic paradigms. These insights have the potential to enhance efforts to combat neurointestinal diseases and may lead to interventions that could alleviate or even reverse these conditions.

The Crucial Role of the Interstitial Cells of Cajal in Neurointestinal Diseases.

Restricted gastric motor functions contribute to aging-associated undernutrition, sarcopenia, and frailty. We previously identified a decline in interstitial cells of Cajal (ICC; gastrointestinal pacemaker and neuromodulator cells) and their stem cells (ICC-SC) as a key factor of gastric aging. Altered functionality of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is central to organismal aging. Here, we investigated the role of EZH2 in the aging-related loss of ICC/ICC-SC.

Inhibition of EZH2 Reduces Aging-Related Decline in Interstitial Cells of Cajal of the Mouse Stomach.

Interstitial cells of Cajal (ICCs), pacemaker and neuromodulator cells in the gastrointestinal (GI) tract, play an important role in GI motility. However, quantifying ICCs is challenging due to their mixed morphologies. Here, we present a protocol for preparing and immunostaining ICC in the murine gastric tunica muscularis using artificial intelligence (AI). We describe steps for obtaining muscles, whole-mount staining, and imaging ICC using confocal microscope. We then detail procedures for training an AI to identify ICCs and quantify their volume. For complete details on the use and execution of this protocol, please refer to Taheri et al..

Protocol for AI-based segmentation and quantification of interstitial cells of Cajal in murine gastric muscle.

Gastrointestinal motor functions are orchestrated by enteric neurons that display a high degree of anatomical and functional variability. Here, we present a protocol for AI-supported immunofluorescence colocalization analysis in human enteric neurons. We describe steps for human gastric tunica muscularis preparation, immunofluorescent labeling of enteric neurons, and quantification of marker colocalization using Nikon NIS-Elements. This protocol addresses the challenges presented by the high density of neurons within enteric ganglia, overlapping fluorescence signals, background fluorescence, and potential user bias in quantification. For complete details on the use and execution of this protocol, please refer to Gao et al..

Article	Year
Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation. Cellular and molecular gastroenterology and hepatology\| PubMed ID: 37301443	2023
The Crucial Role of the Interstitial Cells of Cajal in Neurointestinal Diseases. Biomolecules\| PubMed ID: 37759758	2023
Inhibition of EZH2 Reduces Aging-Related Decline in Interstitial Cells of Cajal of the Mouse Stomach. Cellular and molecular gastroenterology and hepatology\| PubMed ID: 38969206	2024
Protocol for AI-based segmentation and quantification of interstitial cells of Cajal in murine gastric muscle. STAR protocols\| PubMed ID: 39977270	2025
Protocol for AI-supported immunofluorescence colocalization analysis in human enteric neurons. STAR protocols\| PubMed ID: 40382773	2025

Egan L. Choi

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