DOCSLIB.ORG

Human Intestinal M Cells Exhibit Enterocyte-Like Intermediate Filaments

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Human Intestinal M Cells Exhibit Enterocyte-Like Intermediate Filaments 54 Gut 1998;42:54–62 Human intestinal M cells exhibit enterocyte-like intermediate filaments Gut: first published as 10.1136/gut.42.1.54 on 1 January 1998. Downloaded from T Kucharzik, N Lügering, K W Schmid, M A Schmidt, R Stoll, W Domschke Abstract antigens.5612 As M cells have a high capacity Background—The derivation and ul- for transcytosis of a wide range of microorgan- trastructural composition of M cells cov- isms and macromolecules, they are believed to ering the lymphoid follicles of Peyer’s act as an antigen sampling system.34 M cells patches is still unknown. Results from dif- can be characterised electron microscopically ferent animal models have shown that by their characteristic morphology, notably there are species specific diVerences in their atypical microvilli and the presence of an the composition of intermediate filaments invagination of the basolateral membrane har- between M cells and neighbouring entero- bouring leucocytes.47Since the first report on cytes. Little is known, however, about M cells in the human ileum1 and appendix,2 intermediate filaments of human M cells. numerous studies have been done to elucidate Aims—To compare components of the their morphology and to investigate functional cytoskeleton of human M cells with those aspects of M cells in diVerent animal species of adjacent absorptive enterocytes. (for review see Trier7). Little is known, Methods—The expression and localisation however, about the function and morphology of diVerent cytokeratins, vimentin, and of M cells in humans. Concerning their desmin in M cells was determined on folli- morphology, human M cells reveal an anasto- cle associated epithelia of human appen- mosing, short, ridgelike network of folds and dix using immunohistochemistry and occasionally short microvilli in strong contrast immunogold electron microscopy. to the regular appearance of microvilli of adja- Results—Cytokeratins specific for human cent absorptive cells.113 intestinal epithelial cells such as cytok- DiVerent enzymatic markers for the recogni- eratins 8, 18, 19, and 20 were expressed in tion of M cells have been established, such as both absorptive enterocytes and M cells alkaline phosphatase in the brush border.14 with no diVerences in intensity and cellu- Other investigators have determined immuno- lar distribution between both cell types. histochemical markers for M cells, but all are http://gut.bmj.com/ Vimentin and desmin, tissue specific restricted to single animal species. Gebert et al markers of either mesenchymal or myo- have shown that cytokeratin 18 (CK-18) is a genic cells, as well as other cytokeratins sensitive marker for porcine M cells15 while were not detectable in enterocytes or M vimentin is selectively expressed in rabbit M cells. cells.16 M cells in rats are detected by Conclusion—This is the first study on the monoclonal antibodies (clone 4.1.18) raised structure of intermediate filaments in 17 against cytokeratin 8. Allthough all markers on September 28, 2021 by guest. Protected copyright. human intestinal M cells. Our results identified thus far seem to be species specific, show that in contrast to several animal these studies did show that M cells of various models, human M cells apparently do not animals diVer in their composition of cytoskel- diVer from adjacent enterocytes in the eton proteins from adjacent enterocytes. These Department of composition of their intermediate fila- observations suggest that diVerent intermedi- Medicine B ment cytoskeleton. The presence of ente- ate filaments serve variable functions15 16 which T Kucharzik rocyte like cytokeratins and the absence of N Lügering could explain the diVerent properties of M cells W Domschke other cytokeratins as well as of vimentin compared with enterocytes. R Stoll and desmin supports the hypothesis of an Within the system of intermediate filaments, epithelial origin of human intestinal M the subgroup of cytokeratins might serve as a Department of cells and suggests that M cells may derive system of especially potent diVerentiation Pathology from diVerentiated enterocytes. K W Schmid markers, because the diverse patterns of cyto- (Gut 1998;42:54–62) keratin polypeptides are correlated with diVer- Centre for Molecular 18 Keywords: human intestinal M cells; appendix; ent pathways of epithelial diVerentiation. To Biology of cytokeratin; intermediate filaments; follicle associated our knowledge, no data are available concern- Inflammation, epithelium ing the components of the cytoskeleton of University of Münster, Münster, Germany human M cells. There is controversy as to M A Schmidt whether M cells are of epithelial–intestinal or M cells are known as specialised antigen mesenchymal origin. Whether M cells derive Correspondence to: sampling cells that are interspersed between from intestinal crypt cells or from fully Dr T Kucharzik, di erentiated enterocytes and whether this Department of Medicine B, epithelial cells of the follicle associated epithe- V University of Münster, lia (FAE) of the gastrointestinal and respiratory stage in diVerentiation is induced by lymphoid Albert-Schweitzer-Str. 33, tracts.1–7 They diVer morphologically and tissues is also not known. D-48129 Münster, Germany. enzymatically from the adjacent enterocytes, As the properties of specialised M cells in the Accepted for publication show preferential aYnity for certain FAE are diVerent from those of common ente- 16 July 1997 microorganisms,8–11 and take up and transport rocytes, the aim of our study was to investigate Intermediate filaments in human intestinal M cells 55 Table 1 Antibodies Antibody Clone Supplier Dilution Gut: first published as 10.1136/gut.42.1.54 on 1 January 1998. Downloaded from Anticytokeratin 1/2, 10/11 AE2 Progen 1/50 Anticytokeratin 3 AE5 Progen 1/50 Anticytokeratin 4 215B8 Boehringer 1/200 Anticytokeratin 5/6 D5/16B4 Boehringer 1/1000 Anticytokeratin 6 Ks 6KA12 Progen 5 µg/ml Anticytokeratin 7 Ks 7.18 Progen 5 µg/ml Anticytokeratin 8 4.1.18 Boehringer 1/40 Ks 8.7 Progen 5 µg/ml Ks 8.10 Progen 5 µg/ml Anticytokeratin 10/11, 1/2 K8.60 Progen 1/50 Anticytokeratin 13 KS13.1 Progen 1/20 Anticytokeratin 14 LL002 Medac 1/20 Anticytokeratin 16 LL025 Medac 1/40 Anticytokeratin 17 Ks 17.E3 Progen 5 µg/ml Anticytokeratin 18 CY-90 Sigma IH 1/800 EM 1/1000 Ks 18.04 Progen 5 µg/ml Anticytokeratin 19 A53-B/A2 Sigma IH 1/10 EM 1/2 Anticytokeratin 20 Ks 20.10 Progen 1/20 Ks 20.8 Progen 5 µg/ml Anticytokeratin8+18 CAM5.2 Becton-Dickinson 1/2 Antivimentin V9 Immunotech 1/50 Antidesmin DE-R-11 Medac 1/300 IH, immunohistochemistry; EM, immunoelectron microscopy. whether this functional diVerence might be reflected in an unusual range of cytoskeletal proteins. We therefore examined diVerent components of the cytoskeleton in M cells of the human appendix in comparison with adja- cent absorptive enterocytes by immunohisto- chemistry and immunogold electron micros- copy. We determined the expression of tissue specific cytoskeletal proteins such as diVerent cytokeratins, vimentin, an intermediate fila- Figure 2 Photomicrograph of frozen sections of FAE from human appendix. The AP reaction is prominent over the ment protein present in mesenchymal cells, FAE of human appendix but is intermittently broken by and desmin, a marker for myogenic cells in gaps (arrows) (a). Because of the lack of staining for AP, human intestinal M cells. these cells are characterised as M cells. Labelling of the same area with a monoclonal antibody against CK-20 http://gut.bmj.com/ (green fluorescence) shows that there is no diVerence in the staining pattern of M cells and adjacent enterocytes (b). Materials and methods The arrowhead in (a) indicates a goblet cell. Original TISSUE magnification ×400. F,follicle. To examine human intestinal M cells, we used females, nine males; mean age 52 years, range surgical specimens of human appendix. Ap- 27–81) undergoing cystectomy because of car- pendices were obtained from 13 patients (four cinoma of the urinary bladder. All patients gave written informed consent to participate in the on September 28, 2021 by guest. Protected copyright. study. The study protocol was approved by the Human Studies Committee of the University of Münster. Macroscopically and microscopi- cally the appendix was not inflamed in any of the patients investigated. Tissue was taken immediately after resection of the appendix and rinsed with cold Ringer’s solution. Small pieces were fixed overnight at 4°C in 2.5% glutaraldehyde (Serva, Heidel- berg, Germany). Samples that were taken for cryosections were embedded in OCT (Miles, Elkhart, Indiana, USA), snap frozen, and stored in liquid nitrogen. Cryosections were serially cut at –25°C with a Jung Frigocut N2800 (Leica, Nussloch, Germany) (5 µm), fixed in acetone (–20°C) for 10 minutes, and stored at –70°C until use. For paraYn wax sec- tions, the material was fixed in 10% formalde- hyde for 20 hours at room temperature and embedded in paraYn wax. Sections of 2 µm were dewaxed, rehydrated in a series of alcohol, Figure 1 Typical M cell overlying a lymphoid follicle of human appendix embedded in Epon. The surface of the M and transferred to phosphate buVered saline cell (M) shows microfolds and fewer, shorter microvilli than (PBS) (pH 7.2). For morphological evaluation, the adjacent absorptive enterocytes (E). A mononuclear cell the material was stained with haematoxylin in the central hollow (MN) is surrounded by M cell cytoplasm. The cell nucleus (N) is located at the base of the (Merck, Darmstadt, Germany). Sections with M cell (Bar = 0.5 µm). activated lymphoid follicles and corresponding 56 Kucharzik, Lügering, Schmid, et al of alcohol and transferred to PBS (pH 7.2). The sections were blocked with 50% goat serum containing 0.1% bovine serum albumin (BSA) in PBS for one hour and then incubated Gut: first published as 10.1136/gut.42.1.54 on 1 January 1998.
Load more

Recommended publications
  • A Comparative Study of the Ultrastructure of Microvilli in the Epithelium of Small and Large Intestine of Mice
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central A COMPARATIVE STUDY OF THE ULTRASTRUCTURE OF MICROVILLI IN THE EPITHELIUM OF SMALL AND LARGE INTESTINE OF MICE T. M. MUKHERJEE and A. WYNN WILLIAMS From the Electron Microscope Laboratory, the Departlnent of Pathology, the University of Otago Medical School, Dunedin, New Zealand ABSTRACT A comparative analysis of the fine structure of the microvilli on jejunal and colonic epi- thelial cells of the mouse intestine has been made. The microvilli in these two locations demonstrate a remarkably similar fine structure with respect to the thickness of the plasma membrane, the extent of the filament-free zone, and the characteristics of the microfila- ments situated within the microvillous core. Some of the core microfilaments appear to continue across the plasma membrane limiting the tip of the microvillus. The main differ- ence between the microvilli of small intestine and colon is in the extent and organization of the surface coat. In the small intestine, in addition to the commonly observed thin surface "fuzz," occasional areas of the jejunal villus show a more conspicuous surface coat covering the tips of the microvilli. Evidence has been put forward which indicates that the surface coat is an integral part of the epithelial cells. In contrast to the jejunal epithelium, the colonic epithelium is endowed with a thicker surface coat. Variations in the organization of the surface coat at different levels of the colonic crypts have also been noted. The func- tional significance of these variations in the surface coat is discussed.
    [Show full text]
  • Gastrointestinal Stem Cells in Health and Disease: from Flies to Humans Hongjie Li1,2 and Heinrich Jasper1,*
    © 2016. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2016) 9, 487-499 doi:10.1242/dmm.024232 REVIEW SUBJECT COLLECTION: TRANSLATIONAL IMPACT OF DROSOPHILA Gastrointestinal stem cells in health and disease: from flies to humans Hongjie Li1,2 and Heinrich Jasper1,* ABSTRACT is Barrett’s metaplasia (see Box 1), in which the esophageal The gastrointestinal tract of complex metazoans is highly squamous epithelium acquires properties that are reminiscent of the compartmentalized. It is lined by a series of specialized epithelia gastric or intestinal columnar epithelium. This transformation has that are regenerated by specific populations of stem cells. To maintain been associated with acid reflux disease and is believed to be a cause tissue homeostasis, the proliferative activity of stem and/or progenitor of esophageal adenocarcinomas (Falk, 2002; Hvid-Jensen et al., cells has to be carefully controlled and coordinated with regionally 2011). Dysplasia (see Box 1), another type of epithelial lesion that distinct programs of differentiation. Metaplasias and dysplasias, commonly affects the human GI tract, is characterized by aberrant precancerous lesions that commonly occur in the human cell proliferation and differentiation. Dysplastic changes are often gastrointestinal tract, are often associated with the aberrant found at later stages during epithelial carcinogenesis than are proliferation and differentiation of stem and/or progenitor cells. The metaplasias, and eventually lead to invasive carcinoma (see Box 1) increasingly sophisticated characterization of stem cells in the (Correa and Houghton, 2007; Ullman et al., 2009). Much remains to gastrointestinal tract of mammals and of the fruit fly Drosophila has be learnt about intestinal metaplasias and dysplasias, not least provided important new insights into these processes and into the because of their clinical significance, such as the exact cellular mechanisms that drive epithelial dysfunction.
    [Show full text]
  • Study of Mucin Turnover in the Small Intestine by in Vivo Labeling Hannah Schneider, Thaher Pelaseyed, Frida Svensson & Malin E
    www.nature.com/scientificreports OPEN Study of mucin turnover in the small intestine by in vivo labeling Hannah Schneider, Thaher Pelaseyed, Frida Svensson & Malin E. V. Johansson Mucins are highly glycosylated proteins which protect the epithelium. In the small intestine, the goblet Received: 23 January 2018 cell-secreted Muc2 mucin constitutes the main component of the loose mucus layer that traps luminal Accepted: 26 March 2018 material. The transmembrane mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering Published: xx xx xxxx intestinal epithelial cells. Our study aimed at investigating the turnover of these mucins in the small intestine by using in vivo labeling of O-glycans with N-azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrifced every hour up to 12 hours and at 24 hours. Samples were fxed with preservation of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed stable expression over time at the plasma membrane on villi tips, in crypts and at crypt openings. In conclusion, we have identifed diferent subtypes of goblet cells based on their rate of mucin biosynthesis and secretion. In order to protect the intestinal epithelium from chemical and bacterial hazards, fast and frequent renewal of the secreted mucus layer in the villi area is combined with massive secretion of stored Muc2 from goblet cells in the upper crypt. Te small intestinal epithelium is constantly aiming to balance efective nutritional uptake with minimal damage due to exposure to ingested, secreted and resident agents.
    [Show full text]
  • Antenatal Diagnosis of Microvillus Inclusion Disease
    Obstetrics & Gynecology International Journal Case Report Open Access Antenatal diagnosis of microvillus inclusion disease Abstract Volume 12 Issue 4 - 2021 Microvillus inclusion disease is a rare autosomal recessive disorder due to defective apical Gular Israfilova, Banu Arslanca, Yavuz Emre surface of the enterocytes presenting with severe watery diarrhea starting at birth. We describe a female infant who had antenatal diagnosis of microvillus inclusion disease. At Sukur, Acar Koç Department of Obstetrics and Gynecology, Ankara University 36th gestational week of a 32-year-old woman ultrasound examination revealed dilatation of School of Medicine, Turkey fetal sigmoid colon. The amniotic fluid level was normal. An amniocentesis was performed to rule out congenital sodium and chloride diarrhea in the prenatal period. The patient didn’t Correspondence: Gular Israfilova, MD, Ankara University prefer to undergo genetic tests. In conclusion, prenatal ultrasonographic identification of School of Medicine, Department of Obstetrics and Gynecology, dilated bowel loops without polyhydramnios suggests differential diagnosis of microvillus Dikimevi, Ankara, Turkey, Tel 0090 5375752340, inclusion disease in addition to congenital chloride diarrhea, jejunoileal atresia, volvulus, Email meconium ileus, Hirschsprung disease, enteric duplications, anorectal atresia. Received: July 29, 2021 | Published: August 12, 2021 Keywords: congenital diarrhea, microvillus inclusion disease, prenatal diagnosis Introduction respectively. On postpartum 3rd day, the neonate suffered from watery diarrhea and abdominal distension. Abdominal X-ray showed dilated Microvillus inclusion disease (MVID) is a congenital bowel intestinal loops and pneumoperitoneum (Figure 2). On postpartum 5th disease characterized by severe diarrhea, malabsorption and day, the infant was referred to the gastroenterology department due to 1 growth retardation in infancy. Severe watery diarrhea begins in the 19% weight loss.
    [Show full text]
  • 1999, a Cluster of Microvillous Inclusion Disease in the Navajo
    A cluster of microvillous inclusion disease in the Navajo population John F. Pohl, MD, Mitchell D. Shub, MD, Eric E. Trevelline, MD, Kristy Ingebo, MD, Gary Silber, MD, ANancy Rayhorn, RN, BSN, Steve Holve, MD, and Diana Hu, MD riod.1 The prognosis is generally poor, We report 4 unrelated patients with characteristic microscopic findings of with most patients dying by the second microvillous inclusion disease (MID) with early-onset phenotype. All 4 pa- decade of life as a result of complica- tients came from the Navajo reservation in northern Arizona. A literature tions of parenteral alimentation includ- 4 search revealed a fifth unrelated Navajo child with MID. The unusually ing liver failure or sepsis. Various high incidence in this population indicates that a founder effect might be re- treatments including glucocorticoids, sponsible for an increased frequency of this rare genetic disorder in the pentagastrin, human epidermal growth factor, disodium cromoglycate, adreno- Navajo. It is recommended that all Navajo infants presenting with severe corticotropic hormone, prednisolone, diarrhea during early infancy undergo investigation for MID. (J Pediatr and elemental formula feedings have 1999;134:103-6) failed.5-7 However, somatostatin, which is not universally successful,8 reduced stool output in 2 patients,9,10 with an increased weight velocity Microvillous inclusion disease, a rare children with a specific subset of in- noted in 1.10 Loperamide has only disorder with an unknown cause, re- tractable diarrhea and described com- transiently decreased stool output.1 sults in an intractable secretory diar- plete villous atrophy, crypt hypoplasia, Three patients have received intestinal rhea that begins in early infancy.
    [Show full text]
  • The Small and Large Intestines∗
    OpenStax-CNX module: m46512 1 The Small and Large Intestines∗ OpenStax College This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 3.0y Abstract By the end of this section, you will be able to: • Compare and contrast the location and gross anatomy of the small and large intestines • Identify three main adaptations of the small intestine wall that increase its absorptive capacity • Describe the mechanical and chemical digestion of chyme upon its release into the small intestine • List three features unique to the wall of the large intestine and identify their contributions to its function • Identify the benecial roles of the bacterial ora in digestive system functioning • Trace the pathway of food waste from its point of entry into the large intestine through its exit from the body as feces The word intestine is derived from a Latin root meaning internal, and indeed, the two organs together nearly ll the interior of the abdominal cavity. In addition, called the small and large bowel, or colloquially the guts, they constitute the greatest mass and length of the alimentary canal and, with the exception of ingestion, perform all digestive system functions. 1 The Small Intestine Chyme released from the stomach enters the small intestine, which is the primary digestive organ in the body. Not only is this where most digestion occurs, it is also where practically all absorption occurs. The longest part of the alimentary canal, the small intestine is about 3.05 meters (10 feet) long in a living person (but about twice as long in a cadaver due to the loss of muscle tone).
    [Show full text]
  • Nanoarchitecture and Dynamics of the Mouse Enteric Glycocalyx Examined by Freeze-Etching Electron Tomography and Intravital Microscopy
    ARTICLE https://doi.org/10.1038/s42003-019-0735-5 OPEN Nanoarchitecture and dynamics of the mouse enteric glycocalyx examined by freeze-etching electron tomography and intravital microscopy Willy W. Sun1,2,5, Evan S. Krystofiak1,5, Alejandra Leo-Macias1, Runjia Cui1, Antonio Sesso3, Roberto Weigert 4, 1234567890():,; Seham Ebrahim4 & Bechara Kachar 1* The glycocalyx is a highly hydrated, glycoprotein-rich coat shrouding many eukaryotic and prokaryotic cells. The intestinal epithelial glycocalyx, comprising glycosylated transmembrane mucins, is part of the primary host-microbe interface and is essential for nutrient absorption. Its disruption has been implicated in numerous gastrointestinal diseases. Yet, due to chal- lenges in preserving and visualizing its native organization, glycocalyx structure-function relationships remain unclear. Here, we characterize the nanoarchitecture of the murine enteric glycocalyx using freeze-etching and electron tomography. Micrometer-long mucin filaments emerge from microvillar-tips and, through zigzagged lateral interactions form a three-dimensional columnar network with a 30 nm mesh. Filament-termini converge into globular structures ~30 nm apart that are liquid-crystalline packed within a single plane. Finally, we assess glycocalyx deformability and porosity using intravital microscopy. We argue that the columnar network architecture and the liquid-crystalline packing of the fila- ment termini allow the glycocalyx to function as a deformable size-exclusion filter of luminal contents. 1 Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. 2 Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD 20740, USA. 3 Sector of Structural Biology, Institute of Tropical Medicine, University of São Paulo, Sao Paulo, SP 05403, Brazil.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • New Developments in Goblet Cell Mucus Secretion and Function
    REVIEW nature publishing group New developments in goblet cell mucus secretion and function GMH Birchenough1, MEV Johansson1, JK Gustafsson1, JH Bergstro¨m1 and GC Hansson1 Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell that can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example, after endocytosis or in response to acetyl choline. However, despite much progress in recent years, our understanding of goblet cell function and regulation is still in its infancy. THE INTESTINE system of mucus covering the epithelium. There is a The gastrointestinal tract is a remarkable organ. Not only can it two-layered mucus system in the stomach and colon and a digest most of our food into small components, but it is also single-layered mucus in the small intestine.5 The mucus layers filled with kilograms of microbes that live in stable equilibrium in these three regions perform their protective function using with us and our immune system.
    [Show full text]
  • The Transcriptional Repressor Blimp1/Prdm1 Regulates Postnatal Reprogramming of Intestinal Enterocytes
    The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes James Harpera, Arne Moulda, Robert M. Andrewsb, Elizabeth K. Bikoffa, and Elizabeth J. Robertsona,1 aSir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and bWellcome Trust Sanger Institute, Genome Campus, Hinxton-Cambridge CB10 1SA, United Kingdom Edited by Brigid L. M. Hogan, Duke University Medical Center, Durham, NC, and approved May 19, 2011 (received for review April 13, 2011) Female mammals produce milk to feed their newborn offspring rise to the developing crypts. The crypt derived adult enterocytes before teeth develop and permit the consumption of solid food. that emerge at postnatal day (P) 12 and repopulate the entire Intestinal enterocytes dramatically alter their biochemical signature epithelium lack Blimp1 expression. Conditional inactivation of during the suckling-to-weaning transition. The transcriptional re- Blimp1 results in globally misregulated gene expression patterns, pressor Blimp1 is strongly expressed in immature enterocytes in and compromises small intestine (SI) tissue architecture, nutrient utero, but these are gradually replaced by Blimp1− crypt-derived uptake, and survival of the neonate. In combination with tran- adult enterocytes. Here we used a conditional inactivation strategy scriptional profiling, the present experiments demonstrate that to eliminate Blimp1 function in the developing intestinal epithe- Blimp1/Prdm1 orchestrates orderly and extensive reprogramming lium. There was no noticeable effect on gross morphology or of the postnatal intestinal epithelium. formation of mature cell types before birth. However, survival of mutant neonates was severely compromised. Transcriptional Results profiling experiments reveal global changes in gene expression Down-Regulated Blimp1 Expression in Crypt Progenitors Beginning at patterns.
    [Show full text]
  • The Intestinal Stem Cell
    Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The intestinal stem cell Nick Barker, Marc van de Wetering, and Hans Clevers1 Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, the Netherlands The epithelium of the adult mammalian intestine is in a Claudinot et al. 2005). Of note, multipotency can only be constant dialog with its underlying mesenchyme to di- definitively demonstrated when transplantation can be rect progenitor proliferation, lineage commitment, ter- performed with a single cell, which is rarely possible. As minal differentiation, and, ultimately, cell death. The an alternative strategy, candidate stem cells are geneti- epithelium is shaped into spatially distinct compart- cally marked in situ, after which the introduced marker ments that are dedicated to each of these events. While allows the visualization of the modified stem cell and its the intestinal epithelium represents the most vigorously clonal offspring over time. As an example of the latter renewing adult tissue in mammals, the stem cells that approach, a progesterone-responsive version of the Cre fuel this self-renewal process have been identified only recombinase enzyme was specifically expressed in cells recently. The unique epithelial anatomy makes the in- residing in the bulge region of hair follicles using a trans- testinal crypt one of the most accessible models for the genic Keratin-15 promoter (Morris et al. 2004). Activa- study of adult stem cell biology. This review attempts to tion of the Cre enzyme by progesterone irreversibly ac- provide a comprehensive overview of four decades of re- tivated the genetic marker R26R-LacZ in the bulge cells.
    [Show full text]
  • Intestinal Organoids Generated from Human Pluripotent Stem Cells
    DOI: 10.31662/jmaj.2019-0027 https://www.jmaj.jp/ Review Article Intestinal Organoids Generated from Human Pluripotent Stem Cells Satoru Tsuruta1),2), Hajime Uchida3), and Hidenori Akutsu2) Abstract: The gastrointestinal system is one of the most complex organ systems in the human body, and consists of numerous cell types originating from three germ layers. To understand intestinal development and homeostasis and elucidate the patho- genesis of intestinal disorders, including unidentified diseases, several in vitro models have been developed. Human pluripo- tent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have remarkable developmental plasticity and possess the potential for a wide variety of applications. Three-dimensional organs, termed organoids and produced in vitro by PSCs, contain not only epithelium but also mesenchymal tissue and partially recapitu- late intestinal functions. Such intestinal organoids have begun to be applied in disease models and drug development and have contributed to a detailed analysis of molecular interactions and findings in the synergistic development of biomedicine for human digestive organs. In this review, we describe gastrointestinal organoid technology derived from PSCs and consid- er its potential applications. Key Words: intestinal organoids, embryonic stem cells, induced pluripotent stem cells, gastrointestinal disease, drug discovery Introduction the anterior to posterior axis. Accompanied by the develop- ment of the fetus, repeated gut
    [Show full text]