Review

Authors: Laura M Carlson, Neeta L Vora

The American Congress of Obstetricians and Gynecologists recommends that all pregnant women be offered aneuploidy screening or diagnostic testing. A myriad of screening and testing options are available to patients based on their risk profile and gestational age. Screening options include traditional serum analyte screening, such as first-trimester screening or quadruple screening, and more recently, cell-free DNA. Diagnostic testing choices include chorionic villus sampling and amniocentesis. The number of screening and diagnostic modalities complicates prenatal counseling for physicians and can be difficult for patients to grasp. Appropriate pretest and posttest counseling is important to ensure adequate understanding of results and ensure testing strategy is concordant with patient goals.

Topics: Amniocentesis; Aneuploidy; Chorionic Villi Sampling; Counseling; Female; Genetic Testing; Humans; Mass Screening; Pregnancy; Prenatal Diagnosis

PubMed: 28499534
DOI: 10.1016/j.ogc.2017.02.004

Authors: Joep Beumer, Jens Puschhof, Fjodor Yousef Yengej...

Intestinal epithelial cells derive from stem cells at the crypt base and travel along the crypt-villus axis to die at the villus tip. The two dominant villus epithelial cell types, absorptive enterocytes and mucous-secreting goblet cells, are mature when they exit crypts. Murine enterocytes switch functional cell states during migration along the villus. Here, we ask whether this zonation is driven by the bone morphogenetic protein (BMP) gradient, which increases toward the villus. Using human intestinal organoids, we show that BMP signaling controls the expression of zonated genes in enterocytes. We find that goblet cells display similar zonation involving antimicrobial genes. Using an inducible Bmpr1a knockout mouse model, we confirm that BMP controls these zonated genes in vivo. Our findings imply that local manipulation of BMP signal strength may be used to reset the enterocyte "rheostat" of carbohydrate versus lipid uptake and to control the antimicrobial response through goblet cells.

Topics: Animals; Bone Morphogenetic Proteins; Cell Differentiation; Enterocytes; Goblet Cells; Intestinal Mucosa; Intestine, Small; Mice

PubMed: 35235783
DOI: 10.1016/j.celrep.2022.110438

Authors: Andreas E Moor, Yotam Harnik, Shani Ben-Moshe...

The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterium-rich environment. It is unknown whether these tasks are spatially zonated along the villus axis. Here, we extracted a large panel of landmark genes characterized by transcriptomics of laser capture microdissected villus segments and utilized it for single-cell spatial reconstruction, uncovering broad zonation of enterocyte function along the villus. We found that enterocytes at villus bottoms express an anti-bacterial gene program in a microbiome-dependent manner. They next shift to sequential expression of carbohydrates, peptides, and fat absorption machineries in distinct villus compartments. Finally, they induce a Cd73 immune-modulatory program at the villus tips. Our approach can be used to uncover zonation patterns in other organs when prior knowledge of landmark genes is lacking.

Topics: Animals; Cell Differentiation; Cell Movement; Enterocytes; Male; Mice; Mice, Inbred C57BL; Single-Cell Analysis; Transcriptome

PubMed: 30270040
DOI: 10.1016/j.cell.2018.08.063

Review

Authors: Arzu Ensari, Michael N Marsh

The small intestinal villus and its associated epithelium includes enterocytes as the main cell type and differentiated goblet and argentaffin cells, while the invaginated crypt epithelium is the site of cell division and hence the origin of all epithelial components. Enterocytes form a cohesive monolayer which acts both as a permeability barrier between lumen and the interior, and an important gateway for nutrient digestion, absorption and transport. Differentiation and polarisation of enterocytes depends on cytoskeletal proteins that control cell shape and maintain functionally specialised membrane domains; extracellular matrix (ECM) receptors; channels and transporters regulating ion/solute transfer across the cell. The mesenchymally-derived basement membrane dynamically controls morphogenesis, cell differentiation and polarity, while also providing the structural basis for villi, crypts and the microvasculature of the lamina propria so that tissue morphology, crucially, is preserved in the absence of epithelium. Mucosal re-organisation requires immense cooperation between all elements within the lamina, including marked revisions of the microvasculature and extensive alterations to all basement membranes providing support for endodermal and mesenchymal components. In this context, subepithelial myofibroblasts fulfil important regulatory activities in terms of tissue morphogenesis; remodelling; control of epithelial cell development, polarity and functional attributes; and an intimate involvement in repair, inflammation and fibrosis. This paper reviews the main structural and functional aspects of the villus, including the epithelium and its outer glycocalyx and microvillous border; and subjacent to the epithelium, the basement membrane with its attached web of myo-fibroblasts together with the lamina propria core of the villi, and its microvasculature and lacteals. Finally, some comments on the rapidity with which the overall structure of the villi changes in their response to both external, and internal, influences.

PubMed: 30013740
DOI: No ID Found

Authors: De Xin Dang, Haeun Lee, Seung Jae Lee...

INTRODUCTION

The objective of this study was to investigate the effects of dietary supplementation of tributyrin and anise mixture (TA) on growth performance, apparent nutrient digestibility, fecal noxious gas emission, fecal score, jejunal villus height, hematology parameters, and fecal microbiota of weaned pigs.

METHODS

A total of 150 21-day-old crossbred weaned pigs [(Landrace × Yorkshire) × Duroc] were used in a randomized complete block design experiment. All pigs were randomly assigned to 3 groups based on the initial body weight (6.19 ± 0.29 kg). Each group had 10 replicate pens with 5 pigs (three barrows and two gilts) per pen. The experimental period was 42 days and consisted of 3 phases (phase 1, days 1-7; phase 2, days 8-21; phase 3, days 22-42). Dietary treatments were based on a corn-soybean meal-basal diet and supplemented with 0.000, 0.075, or 0.150% TA.

RESULTS AND DISCUSSION

We found that dietary supplementation of graded levels of TA linearly improved body weight, body weight gain, average daily feed intake, and feed efficiency ( < 0.05). TA supplementation also had positive effects on apparent dry matter, crude protein, and energy digestibility ( < 0.05) and jejunal villus height ( < 0.05). The emission of ammonia from feces decreased linearly with the dose of TA increased ( < 0.05). Moreover, TA supplementation was capable to regulate the fecal microbiota diversity, manifesting in a linearly increased Chao1 index and observed species and a linearly decreased Pielou's index ( < 0.05). The abundance of were increased, while the abundance of was decreased, by treatment ( < 0.05). Therefore, we speculated that TA supplementation would improve growth performance and reduce fecal ammonia emission through improving nutrient digestibility, which was attributed to the increase of jejunal villus height and the regulation of fecal microbiota.

PubMed: 36777676
DOI: 10.3389/fvets.2023.1107149

Authors: Takahiro E Ohara, Marco Colonna, Thaddeus S Stappenbeck...

Loss of differentiated cells to tissue damage is a hallmark of many diseases. In slow-turnover tissues, long-lived differentiated cells can re-enter the cell cycle or transdifferentiate to another cell type to promote repair. Here, we show that in a high-turnover tissue, severe damage to the differentiated compartment induces progenitors to transiently acquire a unique transcriptional and morphological postmitotic state. We highlight this in an acute villus injury model in the mouse intestine, where we identified a population of progenitor-derived cells that covered injured villi. These atrophy-induced villus epithelial cells (aVECs) were enriched for fetal markers but were differentiated and lineage committed. We further established a role for aVECs in maintaining barrier integrity through the activation of yes-associated protein (YAP). Notably, loss of YAP activity led to impaired villus regeneration. Thus, we define a key repair mechanism involving the activation of a fetal-like program during injury-induced differentiation, a process we term "adaptive differentiation."

Topics: Adaptation, Biological; Adaptor Proteins, Signal Transducing; Animals; Cell Cycle; Cell Cycle Proteins; Cell Dedifferentiation; Cell Differentiation; Cell Proliferation; Epithelial Cells; Female; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Models, Animal; Phosphoproteins; Regeneration; Signal Transduction; Stem Cells; Wound Healing; YAP-Signaling Proteins

PubMed: 35016013
DOI: 10.1016/j.devcel.2021.12.012

Authors: Huansheng Yang, Xia Xiong, Xiaocheng Wang...

The intestinal upper villus epithelial cells represent the differentiated epithelial cells and play key role in digesting and absorbing lumenal nutrients. Weaning stress commonly results in a decrease in villus height and intestinal dysfunction in piglets. However, no study have been conducted to test the effects of weaning on the physiology and functions of upper villus epithelial cells. A total of 40 piglets from 8 litters were weaned at 14 days of age and one piglet from each litter was killed at 0 d (w0d), 1 d (w1d), 3 d (w3d), 5 d (w5d), and 7 d (w7d) after weaning, respectively. The upper villus epithelial cells in mid-jejunum were isolated using the distended intestinal sac method. The expression of proteins in upper villus epithelial cells was analyzed using the isobaric tags for relative and absolute quantification or Western blotting. The expression of proteins involved in energy metabolism, Golgi vesicle transport, protein amino acid glycosylation, secretion by cell, transmembrane transport, ion transport, nucleotide catabolic process, translational initiation, and epithelial cell differentiation and apoptosis, was mainly reduced during the post-weaning period, and these processes may be regulated by mTOR signaling pathway. These results indicated that weaning inhibited various cellular processes in jejunal upper villus epithelial cells, and provided potential new directions for exploring the effects of weaning on the functions of intestine and improving intestinal functions in weaning piglets.

Topics: Animals; Animals, Newborn; Biological Transport; Down-Regulation; Energy Metabolism; Epithelial Cells; Glycosylation; Intestine, Small; Jejunum; Microvilli; Proteins; Signal Transduction; Sus scrofa; Up-Regulation; Weaning

PubMed: 27022727
DOI: 10.1371/journal.pone.0150216

Authors: Linda Berková, Hassan Fazilaty, Qiutan Yang...

The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.

Topics: Enterocytes; Ligands; Intestinal Mucosa; Transforming Growth Factor beta; Bone Morphogenetic Proteins; Cell Differentiation

PubMed: 37493498
DOI: 10.15252/embr.202256454

Authors: Vassily I Kutyavin, Lisa L Korn, Ruslan Medzhitov...

Eosinophils are well recognized as effector cells of type 2 immunity, yet they also accumulate in many tissues under homeostatic conditions. However, the processes that govern homeostatic eosinophil accumulation and tissue-specific adaptation, and their functional significance, remain poorly defined. Here, we investigated how eosinophils adapt to the small intestine (SI) microenvironment and the local signals that regulate this process. We observed that eosinophils gradually migrate along the crypt-villus axis, giving rise to a villus-resident subpopulation with a distinct transcriptional signature. Retinoic acid signaling was specifically required for maintenance of this subpopulation, while IL-5 was largely dispensable outside of its canonical role in eosinophil production. Surprisingly, we found that a high-protein diet suppressed the accumulation of villus-resident eosinophils. Purified amino acids were sufficient for this effect, which was a consequence of accelerated eosinophil turnover within the tissue microenvironment and was not due to altered development in the bone marrow. Our study provides insight into the process of eosinophil adaptation to the SI, highlighting its reliance on nutrient-derived signals.

Topics: Eosinophils; Bone Marrow; Intestine, Small; Lymphocytes; Tretinoin

PubMed: 38271336
DOI: 10.1073/pnas.2316446121