Stratified layer analysis reveals intrinsic leptin stimulates cryptal mesenchymal cells for controlling mucosal inflammation

Matsumura, Seiichi; Kurashima, Yosuke; Murasaki, Sayuri; Morimoto, Masako; Arai, Fujimi; Saito, Yukinobu; Kim, Dayoung; Inagaki, Yutaka; Kudo, Toshifumi; Ernst, Peter B.; Shimizu, Toshiaki; Kiyono, Hiroshi

doi:10.1038/s41598-020-75186-3

Cited by 8 publications

(9 citation statements)

References 54 publications

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“…Among these potential telocyte marker genes, we found elevated expression at the FAE top of Lepr, encoding the leptin receptor (Fig 4A-B). Lepr was previously shown to be elevated in crypt mesenchymal cells in the colon [26]. Using smFISH combined with immunostaining for PDGFRα, we validated that FAE top telocytes express significantly higher levels of Lepr compared to the FAE bottom and adjacent villus bottom (Fig 4C , F).…”

Section: Fae Top Telocytes Are Marked By Lepr and Are Distinct From Villus Tip Telocytessupporting

confidence: 61%

Spatial expression programs of the intestinal follicle-associated epithelium

Cohen

Massalha

Ben‐Moshe

et al. 2021

Preprint

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The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte anti-microbial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ sub-epithelial telocytes at the FAE top, which are distinct from villus-tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.

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Section: Fae Top Telocytes Are Marked By Lepr and Are Distinct From Villus Tip Telocytessupporting

confidence: 61%

Spatial expression programs of the intestinal follicle-associated epithelium

Cohen

Massalha

Ben‐Moshe

et al. 2021

Preprint

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“…The GI wall consists of mucous, submucous, muscular, and serosal layers ( Matsumura et al, 2020 ). Epithelial cells, M-cells, ECs, goblet cells, and other enteroendocrine cells are located in the mucous layer.…”

Section: Functions Of Enterochromaffin Cells-derived 5-hydroxytryptam...mentioning

confidence: 99%

Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome

Tao

Zhu

et al. 2022

Front. Cell. Neurosci.

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Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.

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“…In addition, leptin was found to be involved in the proliferation of ISCs and the protection and repair of mucosal damage because the expression of Wnt2b was significantly lower in crypt mesenchymal cells than in controls. These results demonstrate the significance of Lepr signalling for the expression of Wnt2b, which is required for the survival and proliferation of ISCs [ 78 ].…”

Section: Hormonal Influence On Intestinal Stem Cellsmentioning

confidence: 78%

“…The proliferation of ISCs near the base of the epithelial crypt is necessary for the regeneration of epithelial cells, and mesenchymal cells that surround these stem cells strictly control their maintenance and development. WNTs, gremlin (GREM) and BMP, which are crucial for intestinal renewal and stem cell maintenance, are secreted by several subpopulations of mesenchymal cells, such as intraepithelial myofibroblasts, GLI family zinc finger 1 + (Gli1+) fibroblasts and telocytes [ 78 ]. Leptin receptors are highly expressed on the surface of crypt MSCs, which suggests that endogenous leptin is an important factor in the control of MSC activity, especially in the crypt, based on the gene expression profile of crypt MSCs.…”

Section: Hormonal Influence On Intestinal Stem Cellsmentioning

confidence: 99%

Effects of hormones on intestinal stem cells

Liu

Zhang

et al. 2023

Stem Cell Res Ther

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The maintenance of intestinal renewal and repair mainly depends on intestinal stem cells (ISCs), which can also contribute to the growth of intestinal tumours. Hormones, which are vital signalling agents in the body, have various effects on the growth and replacement of intestinal stem cells. This review summarises recent progress in the identification of hormones associated with intestinal stem cells. Several hormones, including thyroid hormone, glucagon-like peptide-2, androgens, insulin, leptin, growth hormone, corticotropin-releasing hormone and progastrin, promote the development of intestinal stem cells. However, somatostatin and melatonin are two hormones that prevent the proliferation of intestinal stem cells. Therefore, new therapeutic targets for the diagnosis and treatment of intestinal illnesses can be identified by examining the impact of hormones on intestinal stem cells.

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Stratified layer analysis reveals intrinsic leptin stimulates cryptal mesenchymal cells for controlling mucosal inflammation

Cited by 8 publications

References 54 publications

Spatial expression programs of the intestinal follicle-associated epithelium

Spatial expression programs of the intestinal follicle-associated epithelium

Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome

Effects of hormones on intestinal stem cells

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