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Cells
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The Role of Intestinal Epithelial Cells in Health and Disease
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The Role of Intestinal Epithelial Cells in Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 8275

Special Issue Editor

Dr. Natalia Soshnikova

E-Mail Website
Guest Editor
Institute for Molecular Medicine and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
Interests: stem cells; chromatin and gene regulation; signaling; enteroendocrine cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite you to submit your latest research for this Special Issue of Cells that will be dedicated to “The Role of Intestinal Epithelial Cells in Health and Disease.” This Special Issue will address two main topics. The first topic is the barrier function of the intestinal epithelial cells (IECs). IECs are constantly challenged by food-borne and microbial antigens. In collaboration with endothelial cells and pericytes, epithelial cells establish a gut–vascular barrier (GVB), which coordinates an appropriate innate immune response to injury and infection. A decline in the epithelial cell barrier is a major step in the development of inflammatory bowel disease (IBD).

The second theme is the functions of IECs in the initiation and progression of metabolic diseases, including diabetes and obesity. Enteroendocrine cells sense nutritional signals and release hormones promoting insulin secretion. Furthermore, IECs act as sensors for microbial and diet-derived metabolites. These metabolites modulate epithelial cells, which consecutively regulate immune cells, adipocytes and the nervous system.

Dr. Natalia Soshnikova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • intestinal epithelial cells
  • enteroendocrine cells
  • gut–vascular barrier
  • gut–brain axis
  • inflammation
  • innate immune cells
  • microbiota
  • metabolic diseases
  • cancer

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Published Papers (5 papers)

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Research

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25 pages, 8468 KiB  
Article
Identification and Characterization of Multiple Paneth Cell Types in the Mouse Small Intestine
by Steven Timmermans, Charlotte Wallaeys, Natalia Garcia-Gonzalez, Lotte Pollaris, Yvan Saeys and Claude Libert
Cells 2024, 13(17), 1435; https://doi.org/10.3390/cells13171435 - 27 Aug 2024
Viewed by 607
Abstract
The small intestinal crypts harbor secretory Paneth cells (PCs) which express bactericidal peptides that are crucial for maintaining intestinal homeostasis. Considering the diverse environmental conditions throughout the course of the small intestine, multiple subtypes of PCs are expected to exist. We applied single-cell [...] Read more.
The small intestinal crypts harbor secretory Paneth cells (PCs) which express bactericidal peptides that are crucial for maintaining intestinal homeostasis. Considering the diverse environmental conditions throughout the course of the small intestine, multiple subtypes of PCs are expected to exist. We applied single-cell RNA-sequencing of PCs combined with deep bulk RNA-sequencing on PC populations of different small intestinal locations and discovered several expression-based PC clusters. Some of these are discrete and resemble tuft cell-like PCs, goblet cell (GC)-like PCs, PCs expressing stem cell markers, and atypical PCs. Other clusters are less discrete but appear to be derived from different locations along the intestinal tract and have environment-dictated functions such as food digestion and antimicrobial peptide production. A comprehensive spatial analysis using Resolve Bioscience was conducted, leading to the identification of different PC’s transcriptomic identities along the different compartments of the intestine, but not between PCs in the crypts themselves. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells in Health and Disease)
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12 pages, 2627 KiB  
Article
Endogenous Hyaluronan Promotes Intestinal Homeostasis and Protects against Murine Necrotizing Enterocolitis
by Jeffery V. Eckert, Karni S. Moshal, Kathryn Burge, Adam Wilson and Hala Chaaban
Cells 2024, 13(14), 1179; https://doi.org/10.3390/cells13141179 - 11 Jul 2024
Viewed by 679
Abstract
Necrotizing enterocolitis (NEC) is a complex, multifactorial gastrointestinal disorder predominantly affecting preterm infants. The pathogenesis of this condition involves a complex interplay between intestinal barrier dysfunction, microbial dysbiosis, and an altered immune response. This study investigates the potential role of endogenous hyaluronan (HA) [...] Read more.
Necrotizing enterocolitis (NEC) is a complex, multifactorial gastrointestinal disorder predominantly affecting preterm infants. The pathogenesis of this condition involves a complex interplay between intestinal barrier dysfunction, microbial dysbiosis, and an altered immune response. This study investigates the potential role of endogenous hyaluronan (HA) in both the early phases of intestinal development and in the context of NEC-like intestinal injury. We treated neonatal CD-1 mouse pups with PEP1, a peptide inhibiting HA receptor interactions, from postnatal days 8 to 12. We evaluated postnatal intestinal developmental indicators, such as villi length, crypt depth, epithelial cell proliferation, crypt fission, and differentiation of goblet and Paneth cells, in PEP1-treated animals compared with those treated with scrambled peptide. PEP1 treatment significantly impaired intestinal development, as evidenced by reductions in villi length, crypt depth, and epithelial cell proliferation, along with a decrease in crypt fission activity. These deficits in PEP1-treated animals correlated with increased susceptibility to NEC-like injuries, including higher mortality rates, and worsened histological intestinal injury. These findings highlight the role of endogenous HA in supporting intestinal development and protecting against NEC. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells in Health and Disease)
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19 pages, 20225 KiB  
Article
An Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice
by Christian Vossen, Patricia Schmidt, Claudia Maria Wunderlich, Melanie Joyce Mittenbühler, Claas Tapken, Peter Wienand, Paul Nicolas Mirabella, Leonie Cabot, Anna-Lena Schumacher, Kat Folz-Donahue, Christian Kukat, Ingo Voigt, Jens C. Brüning, Henning Fenselau and F. Thomas Wunderlich
Cells 2024, 13(1), 102; https://doi.org/10.3390/cells13010102 - 4 Jan 2024
Viewed by 2033
Abstract
Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of [...] Read more.
Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of peptides for the control of feeding behavior, glucose metabolism, and gastrointestinal motility. Like all IEC types, EECs are continuously renewed from intestinal stem cells in the crypt base and terminally differentiate into mature subtypes while moving up the crypt–villus axis. Interestingly, EECs adjust their hormonal secretion according to their migration state as EECs receive altering differentiation signals along the crypt–villus axis and thus undergo functional readaptation. Cell-specific targeting of mature EEC subtypes by specific promoters is challenging because the expression of EEC-derived peptides and their precursors is not limited to EECs but are also found in other organs, such as the brain (e.g., Cck and Sst) as well as in the pancreas (e.g., Sst and Gcg). Here, we describe an intersectional genetic approach that enables cell type-specific targeting of functionally distinct EEC subtypes by combining a newly generated Dre-recombinase expressing mouse line (Vil1-2A-DD-Dre) with multiple existing Cre-recombinase mice and mouse strains with rox and loxP sites flanked stop cassettes for transgene expression. We found that transgene expression in triple-transgenic mice is highly specific in I but not D and L cells in the terminal villi of the small intestine. The targeting of EECs only in terminal villi is due to the integration of a defective 2A separating peptide that, combined with low EEC intrinsic Vil1 expression, restricts our Vil1-2A-DD-Dre mouse line and the intersectional genetic approach described here only applicable for the investigation of mature EEC subpopulations. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells in Health and Disease)
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15 pages, 2483 KiB  
Article
TCF7L1 Controls the Differentiation of Tuft Cells in Mouse Small Intestine
by Valeriya V. Zinina, Melanie Sauer, Lira Nigmatullina, Nastasja Kreim and Natalia Soshnikova
Cells 2023, 12(11), 1452; https://doi.org/10.3390/cells12111452 - 23 May 2023
Cited by 1 | Viewed by 1697
Abstract
Continuous and rapid renewal of the intestinal epithelium depends on intestinal stem cells (ISCs). A large repertoire of transcription factors mediates the correct maintenance and differentiation of ISCs along either absorptive or secretory lineages. In the present study, we addressed the role of [...] Read more.
Continuous and rapid renewal of the intestinal epithelium depends on intestinal stem cells (ISCs). A large repertoire of transcription factors mediates the correct maintenance and differentiation of ISCs along either absorptive or secretory lineages. In the present study, we addressed the role of TCF7L1, a negative regulator of WNT signalling, in embryonic and adult intestinal epithelium using conditional mouse mutants. We found that TCF7L1 prevents precocious differentiation of the embryonic intestinal epithelial progenitors towards enterocytes and ISCs. We show that Tcf7l1 deficiency leads to upregulation of the Notch effector Rbp-J, resulting in a subsequent loss of embryonic secretory progenitors. In the adult small intestine, TCF7L1 is required for the differentiation of secretory epithelial progenitors along the tuft cell lineage. Furthermore, we show that Tcf7l1 promotes the differentiation of enteroendocrine D- and L-cells in the anterior small intestine. We conclude that TCF7L1-mediated repression of both Notch and WNT pathways is essential for the correct differentiation of intestinal secretory progenitors. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells in Health and Disease)
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Review

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22 pages, 18013 KiB  
Review
Adenosine in Intestinal Epithelial Barrier Function
by Mariya Stepanova and Carol M. Aherne
Cells 2024, 13(5), 381; https://doi.org/10.3390/cells13050381 - 23 Feb 2024
Cited by 2 | Viewed by 2358
Abstract
At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease [...] Read more.
At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease (IBD), barrier function is compromised, which results in rampant inflammation and tissue injury. In response to the destruction, the intestinal epithelium releases adenosine, a small but powerful nucleoside that functions as an alarm signal. Amidst the chaos of inflammation, adenosine aims to restore order. Within the scope of its effects is the ability to regulate intestinal epithelial barrier integrity. This review aims to define the contributions of adenosine to mucus production, microbiome-dependent barrier protection, tight junction dynamics, chloride secretion and acid–base balance to reinforce its importance in the intestinal epithelial barrier. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells in Health and Disease)
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