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The intestinal lamina propria contains a diverse network of fibroblasts that provide key support functions to cells within their local environment. Despite this, our understanding of the diversity, location and ontogeny of fibroblasts within and along the length of the intestine remains incomplete. Here we show that the small and large intestinal lamina propria contain similar fibroblast subsets that locate in specific anatomical niches. Nevertheless, we find that the transcriptional profile of similar fibroblast subsets differs markedly between the small intestine and colon suggesting region specific functions. We perform in vivo transplantation and lineage-tracing experiments to demonstrate that adult intestinal fibroblast subsets, smooth muscle cells and pericytes derive from Gli1 -expressing precursors present in embryonic day 12.5 intestine. Trajectory analysis of single cell RNA-seq datasets of E12.5 and adult mesenchymal cells suggest that adult smooth muscle cells and fibroblasts derive from distinct embryonic intermediates and that adult fibroblast subsets develop in a linear trajectory from CD81 + fibroblasts. Finally, we provide evidence that colonic subepithelial PDGFRα hi fibroblasts comprise several functionally distinct populations that originate from an Fgfr2 -expressing fibroblast intermediate. Our results provide insights into intestinal stromal cell diversity, location, function, and ontogeny, with implications for intestinal development and homeostasis. Stromal cells are essential for intestinal homeostasis. Here the authors describe the phenotype, transcriptional profile and location of stromal cell subsets in the adult murine small intestine and colon lamina propria and demonstrate that these cells derive from Gli1+ precursors present in embryonic day 12.5 intestine.

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences 1 – 3 . How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases 4 . Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size. High levels of the sexually dimorphic hormone ecdysone, produced by active ovaries in Drosophila , promote the proliferation of stem cells in the female gut and maximize reproductive fitness, but also increase female susceptibility to age-dependent dysplasia and tumorigenesis.

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.

Intestinal tissue made in vitro Using a sequence of growth-factor manipulations to mimic embryonic intestinal development in culture, a new study has successfully generated human intestinal tissue in vitro from embryonic and induced pluripotent stem cells. The resulting epithelium was uniformly intestinal, with villus-like structures and progenitor domains, and contained all of the functional cell types of the gut, including brush borders that were indistinguishable from adult intestine. This approach may provide therapeutic benefit for disease studies. Using a temporal series of growth factor manipulations to mimic embryonic intestinal development in culture, this study has successfully directed the differentiation of human pluripotent stem cells (both embryonic stem cells and induced pluripotent stem cells) into intestinal tissue. This approach may provide therapeutic benefit for disease studies. Studies in embryonic development have guided successful efforts to direct the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into specific organ cell types in vitro 1 , 2 . For example, human PSCs have been differentiated into monolayer cultures of liver hepatocytes and pancreatic endocrine cells 3 , 4 , 5 , 6 that have therapeutic efficacy in animal models of liver disease 7 , 8 and diabetes 9 , respectively. However, the generation of complex three-dimensional organ tissues in vitro remains a major challenge for translational studies. Here we establish a robust and efficient process to direct the differentiation of human PSCs into intestinal tissue in vitro using a temporal series of growth factor manipulations to mimic embryonic intestinal development 10 . This involved activin-induced definitive endoderm formation 11 , FGF/Wnt-induced posterior endoderm pattering, hindgut specification and morphogenesis 12 , 13 , 14 , and a pro-intestinal culture system 15 , 16 to promote intestinal growth, morphogenesis and cytodifferentiation. The resulting three-dimensional intestinal ‘organoids’ consisted of a polarized, columnar epithelium that was patterned into villus-like structures and crypt-like proliferative zones that expressed intestinal stem cell markers 17 . The epithelium contained functional enterocytes, as well as goblet, Paneth and enteroendocrine cells. Using this culture system as a model to study human intestinal development, we identified that the combined activity of WNT3A and FGF4 is required for hindgut specification whereas FGF4 alone is sufficient to promote hindgut morphogenesis. Our data indicate that human intestinal stem cells form de novo during development. We also determined that NEUROG3, a pro-endocrine transcription factor that is mutated in enteric anendocrinosis 18 , is both necessary and sufficient for human enteroendocrine cell development in vitro . PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development and disease.

Niche-free stem-cell organization Sato et al . present a method for establishing long-term culture conditions whereby single stem cells or single crypt structures isolated from intestinal crypts can generate organoids with all the differentiated cell types and architecture of intestinal crypts present in adult mammals. The stem cells they used to start the cultures were marked by Lrg5 + , a protein that in an earlier study had been shown to mark six cycling stem cells that renew the rapidly self-renewing tissue of the intestine. They conclude that intestinal crypt-villus units are self-organizing structures, which can be built from a single stem cell in the absence of a cellular niche. Lrg5 + is a protein which has been shown to mark cycling stem cells that renew the tissue of the intestine. Here, Lrg5 + stem cells were used in the establishment of long-term culture conditions capable of generating organoids with all the cell types and architecture of intestinal crypts present in adult mammals. The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5 + stem cells at the bottoms of small-intestinal crypts 1 . Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5 + stem cells can also initiate these crypt-villus organoids. Tracing experiments indicate that the Lgr5 + stem-cell hierarchy is maintained in organoids. We conclude that intestinal crypt-villus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

The transition to using dual-purpose chickens is an alternative to killing male hatchlings of high performance egg-laying chickens. This study aimed to compare the gastrointestinal tract of a recently developed genetic line of dual purpose male chicken, Lohmann Dual (LD), with that of a broiler line, Ross 308. Eighty birds from each line were grown until they reached an average body weight 2000 g (5 weeks for Ross and 9 for LD birds). Six birds of each line were sampled weekly. Body weight (BW), normalized mass of gastrointestinal segments and relative length of intestine were determined. Histologically the villus height, epithelium height, crypt depth, mucosal enlargement factor and the tunica muscularis thickness were measured in jejunum and ileum. Data were regressed against body weight and genetic line. Jejunal enterocyte microvilli and junctional complexes length were measured. Normalized mass and relative length of the gastrointestinal segments were greater in LD birds than in Ross birds at all ages. After day 7 these decreased steadily over the lifetime of the birds in both genetic lines. The growth curves of the gastrointestinal segments of the LD birds were similar to those of the Ross birds. In birds of the same BW, LD birds had a significantly heavier gizzard, shorter intestine, higher jejunal villi, thicker ileal tunica muscularis and smaller ileal mucosal enlargement factor than were found in Ross birds. The large gizzard in LD chickens presumably increases the degree of food processing and enhances availability of nutrients in the orad part of the intestine leading to a lower nutrient concentration and a smaller absorption surface area in the ileum of the LD compared to the Ross chickens. The anatomical differences between the two lines are important criteria for further selection and should be considered in their feeding management.

Farmed salmon feeds have changed from purely marine-based diets with high levels of EPA and DHA in the 1990s to the current 70 % plant-based diets with low levels of these fatty acids (FA). The aim of this study was to establish the impacts of low dietary EPA and DHA levels on performance and tissue integrity of Atlantic salmon (Salmo salar). Atlantic salmon (50 g) in seawater were fed fourteen experimental diets, containing five levels (0, 0·5, 1·0, 1·5 and 2·0 %) of EPA, DHA or a 1:1 EPA+DHA plus control close to a commercial diet, to a final weight of 400 g. Lack of EPA and DHA did not influence mortality, but the n-3-deficient group exhibited moderately slower growth than those fed levels above 0·5 %. The heart and brain conserved EPA and DHA levels better than skeletal muscle, liver, skin and intestine. Decreased EPA and DHA favoured deposition of pro-inflammatory 20 : 4n-6 and 20 : 3n-6 FA in membrane phospholipids in all tissues. When DHA was excluded from diets, 18 : 3n-3 and EPA were to a large extent converted to DHA. Liver, skeletal and cardiac muscle morphology was normal in all groups, with the exception of cytoplasm packed with large or foamy vacuoles and sometimes swollen enterocytes of intestine in both deficient and EPA groups. DHA supplementation supported normal intestinal structure, and 2·0 % EPA+DHA alleviated deficiency symptoms. Thus, EPA and DHA dietary requirements cannot be based exclusively on growth; tissue integrity and fish health also need to be considered.

Organs have a distinctive yet often overlooked spatial arrangement in the body 1 – 5 . We propose that there is a logic to the shape of an organ and its proximity to its neighbours. Here, by using volumetric scans of many Drosophila melanogaster flies, we develop methods to quantify three-dimensional features of organ shape, position and interindividual variability. We find that both the shapes of organs and their relative arrangement are consistent yet differ between the sexes, and identify unexpected interorgan adjacencies and left–right organ asymmetries. Focusing on the intestine, which traverses the entire body, we investigate how sex differences in three-dimensional organ geometry arise. The configuration of the adult intestine is only partially determined by physical constraints imposed by adjacent organs; its sex-specific shape is actively maintained by mechanochemical crosstalk between gut muscles and vascular-like trachea. Indeed, sex-biased expression of a muscle-derived fibroblast growth factor-like ligand renders trachea sexually dimorphic. In turn, tracheal branches hold gut loops together into a male or female shape, with physiological consequences. Interorgan geometry represents a previously unrecognized level of biological complexity which might enable or confine communication across organs and could help explain sex or species differences in organ function. In fruit flies, three-dimensional organ arrangement is stereotypical, sexually dimorphic and actively maintained by muscle-vessel mechanochemical crosstalk.

Drosophila melanogaster females experience a large shift in energy homeostasis after mating to compensate for nutrient investment in egg production. To cope with this change in metabolism, mated females undergo widespread physiological and behavioral changes, including increased food intake and altered digestive processes. The mechanisms by which the female digestive system responds to mating remain poorly characterized. Here, we demonstrate that the seminal fluid protein Sex Peptide (SP) is a key modulator of female post-mating midgut growth and gene expression. SP is both necessary and sufficient to trigger post-mating midgut growth in females under normal nutrient conditions, and likely acting via its receptor, Sex Peptide Receptor (SPR). Moreover, SP is responsible for almost the totality of midgut transcriptomic changes following mating, including up-regulation of protein and lipid metabolism genes and down-regulation of carbohydrate metabolism genes. These changes in metabolism may help supply the female with the nutrients required to sustain egg production. Thus, we report a role for SP in altering female physiology to enhance reproductive output: Namely, SP triggers the switch from virgin to mated midgut state.

Background Insects in the fish diet are a natural source of protein, fat, and other nutrients. These meals are considered an ecological replacement for fishmeal to improve growth parameters. The application of insect meals to fish diets has been studied, especially in continental fish. Data regarding the effects of insect meals on the gut health of Siberian sturgeon are not available. This study investigated the effects of full-fat Hermetia illucens (HI) and Tenebrio molitor (TM) meals on the gut health of juvenile Siberian sturgeon. Growth performance, gastrointestinal tract (GIT) histomorphology and the microbiome composition of juvenile Siberian sturgeon were analyzed. Results The inclusion of insect meals did not affect the growth performance or the survival rate. In the gastrointestinal tract histomorphology, a reduction in the mucosa thickness with the HI treatment was observed. In contrast, fish fed the TM diet had an increase in the thickness of the muscular layer. There were no observed significant differences in villus height among treatments. The analysis of the selected microbiota populations in the Siberian sturgeon gastrointestinal tract showed that insect addition affected the composition of the microbiome. The greatest effect on bacterial populations ( Clostridium leptum subgroup , Enterobacteriaceae, Clostridium coccoides – Eubacterium rectale cluster, Aeromonas spp., Bacillus spp., Carnobacterium spp., Enterococcus spp. and Lactobacillus group) was observed with the HI diet ( P  < 0.05). The TM-based diet increased counts in the following bacterial groups: Clostridium coccoides – Eubacterium rectale cluster, Bacillus spp., Carnobacterium spp., and Enterococcus spp. In contrast, the TM diet decreased the total number of bacteria . The TM diet did not significantly affect the Clostridium leptum subgroup , Enterobacteriaceae, Aeromonas spp. or the Lactobacillus group. Conclusions Fish meal replacement by the inclusion of 15% of full-fat Hermetia illucens and Tenebrio molitor (15%) meals did not affect the growth performance, survival rate or villus height of juvenile Siberian sturgeon. The present study suggests that an H. illucens- based diet positively affects the gut microbiota composition and intestinal morphology of juvenile Siberian sturgeon without negative changes in the villus height.