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Article
| Open Access
p53 promotes revival stem cells in the regenerating intestine after severe radiation injury
The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.
- Clara Morral
- , Arshad Ayyaz
- & David G. Kirsch
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Article
| Open Access
Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids
Challenges in reproducibility and large-scale expansion limit the current applicability of human intestinal organoids. Here, the authors present a feeder-free, chemically-defined culture method for enrichment of intestinal stem cells isolated from 3D human intestinal organoids.
- Ohman Kwon
- , Hana Lee
- & Mi-Young Son
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Article
| Open Access
IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration
Omrani, Krepelova et al. report that aging-induced proinflammatory IFNγ/Stat1 signalling primes intestinal stem cells to a secretory fate and to antigen presenting cells impairing the regenerative capacity of the aging gut epithelium.
- Omid Omrani
- , Anna Krepelova
- & Francesco Neri
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Article
| Open Access
Host control and the evolution of cooperation in host microbiomes
Humans, and many other species, carry a large set of beneficial microbes. Here, the authors present new theory and data to argue that these vital relationships only work when hosts can control their microbiome and suppress wayward symbionts.
- Connor Sharp
- & Kevin R. Foster
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Article
| Open Access
Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors
Enhancers for endodermal organs are primed at the chromatin level prior to lineage induction by FOXA pioneer transcription factors; how pervasive this is, is not well known. Here the authors show that only a small subset of organ-specific enhancers are bound and primed by FOXA prior to lineage induction, whereas the majority do not undergo chromatin priming and engage FOXA upon lineage induction.
- Ryan J. Geusz
- , Allen Wang
- & Maike Sander
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Article
| Open Access
SARS-CoV-2 infection and replication in human gastric organoids
Several clinical reports have described gastrointestinal symptoms for COVID-19, though whether the virus can replicate within the stomach remains unclear. Here the authors generate gastric organoids from human biopsies and show that the virus can efficiently infect gastric epithelium, suggesting that the stomach might have an active role in fecal-oral transmission.
- Giovanni Giuseppe Giobbe
- , Francesco Bonfante
- & Paolo De Coppi
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Article
| Open Access
Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo
Combining mouse hepatocyte progenitors and cholangiocytes ex vivo, the authors form an organoid that can drain bile ex vivo and transport metabolites, as in the liver.
- Naoki Tanimizu
- , Norihisa Ichinohe
- & Toshihiro Mitaka
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Article
| Open Access
A stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration
Transition zones connect distinct epithelia, contain cells expressing stem cell markers, and contribute to cancer development. Here, the authors examine the mouse anorectal junction, identifying a population of Krt17-positive basal cells that contribute to squamous and glandular epithelia during homeostasis and repair.
- Louciné Mitoyan
- , Véronique Chevrier
- & Géraldine Guasch
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Perspective
| Open Access
A bioengineering perspective on modelling the intestinal epithelial physiology in vitro
Maria Antfolk and Kim Jensen discuss how to model intestinal epithelial cell function in the dish and how various physiologically important environmental conditions, for example, extracellular matrix, pressure and flow, can be modelled and how this is applicable to clinical work.
- Maria Antfolk
- & Kim B. Jensen
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Article
| Open Access
Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport
Enteroendocrine cells (EECs) are specialized gastrointestinal cells that have a role in nutrient sensing and hormone secretion. Here the authors show that peptide YY from EECs regulates nutrient absorption in intestinal organoids.
- Heather A. McCauley
- , Andrea L. Matthis
- & James M. Wells
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Article
| Open Access
Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells
Human induced pluripotent stem cell-derived intestinal organoids (HIOs) are powerful tools to study development and diseases of the gastrointestinal tract. Here, the authors develop a directed differentiation protocol to generate mesenchyme-free HIOs that can be patterned towards proximal small intestine or colonic epithelium, and demonstrated their utility in modeling CFTR function.
- Aditya Mithal
- , Amalia Capilla
- & Gustavo Mostoslavsky
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Article
| Open Access
Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo
The role of the transmembrane glycoprotein CD47 in healing injured intestinal mucosa is unclear. Here, the authors show that selective loss of CD47 in the murine intestinal epithelium results in defective mucosal repair after colonic wounding, with suggested impaired cell migration in vitro.
- Michelle Reed
- , Anny-Claude Luissint
- & Charles A. Parkos
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Article
| Open Access
Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23
Necrotizing enterocolitis (NEC) is associated with severe neonatal morbidity. Here the authors show, mirroring the NEC phenotype, that IL-23 overexpression in neonates causes malabsorption and decreased expression of intestinal and pancreatic genes mediating food digestion and uptake through IL-22, which directly suppresses pancreatic cell differentiation.
- Lili Chen
- , Valentina Strohmeier
- & Glaucia C. Furtado
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Article
| Open Access
Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes
Efforts to determine the effects of drugs on epithelial barriers could benefit from better in vitro models. Here the authors develop a microfluidic device supporting the growth and function of extracellular matrix-supported intestinal tubules, and evaluate the effect of staurosporine and acetylsalicylic acid on barrier integrity.
- Sebastiaan J. Trietsch
- , Elena Naumovska
- & Paul Vulto
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Article
| Open Access
Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease
Metalloproteinase-9 has been suggested as therapeutic target to treat inflammatory bowel disease. Here de Bruynet al. show that genetic and pharmacological inhibition of metalloproteinase-9 does not ameliorate inflammation and fibrosis in mice challenged with acute and chronic colitis protocols.
- Magali de Bruyn
- , Christine Breynaert
- & Ghislain Opdenakker
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Article
| Open Access
Mutual reinforcement between telomere capping and canonical Wnt signalling in the intestinal stem cell niche
Mice lacking telomerase provide a model to study pathogenesis caused by critical telomere shortening. Here, the authors provide evidence that telomere shortening causes downregulation of Wnt signalling in intestinal crypts and that defects can be partially rescued by treatment with Wnt agonists.
- Ting-Lin B. Yang
- , Qijun Chen
- & F. Brad Johnson
LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model