Intestinal stem cells articles within Nature Communications

Featured

• Article
  09 April 2024 | Open Access

  DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells

  Inflammatory bowel disease (IBD) is featured with epithelial barrier dysfunction, however, the underlying mechanism is less clear. Here, the authors show that DHX9 deficiency in intestinal stem cells (ISCs) induces accumulation of abnormal R-loops and subsequent genomic instability, leading to impairment of ISCs and development of IBD.

  • Xingxing Ren
  • , Qiuyuan Liu
  •  & Shu Zhu

• Article
  26 March 2024 | Open Access

  Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor

  The mechanisms underlying cell plasticity remain poorly understood. Here, Guo et.al discover that intestinal cells in the fly gut can alter their fates through the loss of a single gene, and identify several molecular barriers to cell reprogramming.

  • Xingting Guo
  • , Chenhui Wang
  •  & Rongwen Xi

• Article
  02 March 2024 | Open Access

  Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster

  Intestinal physiology requires a balance between stem cell self-renewal and differentiation. Here, the authors show that this balance is regulated epigenetically by a dynamic relationship between the evolutionarily conserved PRC2, miR-8 and Notch signaling.

  • Zoe Veneti
  • , Virginia Fasoulaki
  •  & Aristides G. Eliopoulos

• Article
  27 February 2024 | Open Access

  The emergence of circadian timekeeping in the intestine

  Circadian rhythms are present in cells throughout the body but how these develop is poorly understood. Here, using Drosophila genetics and single cell analysis, authors find that the intestinal clock emerges after development is complete, and that differentiation disrupts its function.

  • Kathyani Parasram
  • , Amy Zuccato
  •  & Phillip Karpowicz

• Article
  16 February 2024 | Open Access

  Mosquito midgut stem cell cellular defense response limits Plasmodium parasite infection

  Here, the authors study the cellular response of midgut progenitors in Anopheles stephensi to Plasmodium berghei infection. They show that midgut stem cells are able to detect Plasmodium oocysts and eliminate them in a Jak/STAT pathway dependent manner.

  • Ana-Beatriz F. Barletta
  • , Jamie C. Smith
  •  & Carolina Barillas-Mury

• Article
  27 January 2024 | 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

• Article
  04 January 2024 | Open Access

  Drosophila activins adapt gut size to food intake and promote regenerative growth

  While activins are critical regulators of early development, their role in maintaining adult tissue homeostasis remains obscure. Here the authors explore the role of activins in promoting intestinal regeneration and nutrient-dependent gut resizing in Drosophila.

  • Christian F. Christensen
  • , Quentin Laurichesse
  •  & Ditte S. Andersen

• Article
  02 January 2024 | Open Access

  p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome

  Radiation induced gastrointestinal syndrome is a complication of radiotherapy and the tumor suppressor p53 is implicated in protection from gastrointestinal toxicity. Here Wang and colleagues show that p53 protection against radiation-induced gastrointestinal syndrome involves intestinal stem cell function and inhibition of inflammation triggered by radiation via the IL12- p40/MHC-II axis.

  • Jianming Wang
  • , Chun-Yuan Chang
  •  & Wenwei Hu

• Article
  20 December 2023 | Open Access

  Adult stem cell activity in naked mole rats for long-term tissue maintenance

  Authors report that long-term intestinal tissue maintenance in naked mole rats is achieved by having an expanded pool of slow-dividing adult stem cells while a higher proportion of differentiated cells confer enhanced function and protection to the intestinal mucosa.

  • Shamir Montazid
  • , Sheila Bandyopadhyay
  •  & Shazia Irshad

• Article
  21 November 2023 | Open Access

  A distinct Acyl-CoA binding protein (ACBP6) shapes tissue plasticity during nutrient adaptation in Drosophila

  Plasticity in tissue function and morphology is shaped by adaptive responses to nutrient changes. Here, the authors found that a putative calibration of acyl-CoA and acetyl-CoA metabolism through ACBP6 is crucial for Drosophila intestine’s proliferative homeostasis in response to nutrient changes.

  • Xiaotong Li
  •  & Jason Karpac

• Article
  25 October 2023 | Open Access

  Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization

  Intestinal ischemia/reperfusion (I/R) injury is a life-threatening problem in surgeries. Here, authors report that intestinal organoids transplantation attenuates intestinal I/R injury in mice through L-Malic acid-mediated M2 macrophage polarization.

  • Fang-Ling Zhang
  • , Zhen Hu
  •  & Ke-Xuan Liu

• Article
  23 October 2023 | Open Access

  Hierarchical assembly of tryptophan zipper peptides into stress-relaxing bioactive hydrogels

  Rational design has endowed self-assembling peptides with structural similarities to natural materials, but recreating the dynamic functional properties inherent to natural systems remains challenging. Here the authors report the discovery of a short peptide based on the tryptophan zipper motif, that shows multiscale hierarchical ordering into hydrogels that display emergent dynamic properties.

  • Ashley K. Nguyen
  • , Thomas G. Molley
  •  & Kristopher A. Kilian

• Article
  23 October 2023 | Open Access

  Phase separation of BuGZ regulates gut regeneration and aging through interaction with m⁶A regulators

  Phase separation serves to compartmentalize and concentrate cellular components to facilitate essential physiological processes. Here, the authors elucidate the role and mechanism of BuGZ-mediated phase separation in the context of gut regeneration and aging.

  • Qiaoqiao Zhang
  • , Kai Deng
  •  & Hao Jiang

• Article
  30 September 2023 | 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

• Article
  05 September 2023 | Open Access

  A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury

  Mechanisms promoting epithelial regeneration after intestinal injury are poorly understood. Here, authors report that intestinal stem cells produce IL-33 after radiation injury, which induces Paneth cells to produce EGF and promote regeneration.

  • Marco Calafiore
  • , Ya-Yuan Fu
  •  & Alan M. Hanash

• Article
  23 June 2023 | Open Access

  Intracellular pH dynamics regulates intestinal stem cell lineage specification

  Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu et al. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell.

  • Yi Liu
  • , Efren Reyes
  •  & Diane L. Barber

• Article
  25 May 2023 | Open Access

  Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche

  Most intestinal organoid models do not accurately model the interactions between epithelial and stromal cells. Here they establish a colon assembloid system with epithelial and stromal cells and demonstrate that BMP signals from differentiating epithelial cells promote mesenchymal niche organization.

  • Manqiang Lin
  • , Kimberly Hartl
  •  & Michael Sigal

• Article
  18 August 2022 | Open Access

  Multiscale light-sheet organoid imaging framework

  Live imaging of organoid growth remains a challenge: it requires long-term imaging of several samples simultaneously and dedicated analysis pipelines. Here the authors report an experimental and image processing framework to turn long-term light-sheet imaging of intestinal organoids into digital organoids.

  • Gustavo de Medeiros
  • , Raphael Ortiz
  •  & Prisca Liberali

• Article
  02 August 2022 | Open Access

  Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation

  Intestinal stem cells are responsible for replenishing cells within the high-turnover intestinal epithelium. Here they show that ribosome dynamics affect intestinal stem cell identity through a mechanism that is triggered by changes in nutrient availability.

  • Joana Silva
  • , Ferhat Alkan
  •  & William James Faller

• Article
  09 July 2022 | Open Access

  Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5⁺ intestinal stem cell function

  Here the authors report that inhibition of de novo fatty acid synthesis by deleting the enzyme Acetyl-CoA-Carboxylase 1 in the intestinal epithelium results in the loss of crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells.

  • Shuting Li
  • , Chia-Wen Lu
  •  & Matthias Lochner

• Article
  03 June 2022 | Open Access

  CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation

  Intestinal stem cells contribute to homeostasis through a balance between self-renewal and differentiation. Here the authors show that CCN1 is an intestinal stem cell niche factor that activates integrin αvβ3/αvβ5 signaling to regulate proliferation and differentiation through distinct downstream pathways.

  • Jong Hoon Won
  • , Jacob S. Choi
  •  & Joon-Il Jun

• Article
  05 April 2022 | Open Access

  Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells

  Rapid intestinal regeneration after injury is critical to maintain barrier integrity and homeostasis, but must be tightly controlled to prevent tumorigenesis. Here they show that the aryl hydrocarbon receptor is required to terminate the regenerative response after wound healing.

  • Kathleen Shah
  • , Muralidhara Rao Maradana
  •  & Brigitta Stockinger

• Article
  21 March 2022 | Open Access

  Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium

  Rapid turnover and regeneration of intestinal epithelium requires distinct intestinal stem cell (ISC) populations. Here the authors show p57 marks quiescent ISCs, and that differentiated cells revert to stem cell state after injury, through dynamic reprogramming characterized by fetal- and metaplastic-like changes.

  • Tsunaki Higa
  • , Yasutaka Okita
  •  & Keiichi I. Nakayama

• Article
  07 February 2022 | Open Access

  Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling

  The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine.

  • Martti Maimets
  • , Marianne Terndrup Pedersen
  •  & Kim B. Jensen

• Article
  11 January 2022 | Open Access

  Robust differentiation of human enteroendocrine cells from intestinal stem cells

  Hormone-producing enteroendocrine cells (EEC) regulate of energy homeostasis and gastrointestinal function. Here the authors report protocols to induce human intestinal stem cells into EECs producing multiple gut hormones, including SST, 5-HT, CCK and GIP, using directed differentiation with small molecules targeting FOXO1, JNK and CB1 signalling.

  • Daniel Zeve
  • , Eric Stas
  •  & David T. Breault

• Article
  18 November 2021 | Open Access

  Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage

  While the role of smooth muscle in peristalsis has been studied extensively, little is known about its other functions in the intestine. Here the authors identify MMP17, expressed by smooth muscle cells, as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

  • Mara Martín-Alonso
  • , Sharif Iqbal
  •  & Menno J. Oudhoff

• Article
  17 September 2021 | Open Access

  A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses

  Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.

  • Joep Beumer
  • , Maarten H. Geurts
  •  & Hans Clevers

• Article
  10 August 2021 | Open Access

  The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium

  RPAP3 is a subunit of the R2TP complex, a co-chaperone of HSP90, with substrate proteins involved in transcription, ribosome biogenesis, DNA repair and cell growth. Here the authors report that deletion of Rpap3 abrogates cell proliferation and homeostasis in mouse intestine, partly through destabilization of PI3K-like kinases, while elevated RPAP3 levels in colorectal tumors are associated with poor prognosis.

  • Chloé Maurizy
  • , Claire Abeza
  •  & Bérengère Pradet-Balade

• Article
  03 June 2021 | Open Access

  Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells

  The identification and characterisation of dormant cells is currently difficult. Here the authors report Optical Stem Cell Activity Reporter (OSCAR) to assess RNA polymerase II activity and identify dormant cell populations in intestinal epithelial cells in vivo.

  • Rasmus Freter
  • , Paola Falletta
  •  & Francesco Neri

• Article
  12 May 2021 | 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

• Article
  01 March 2021 | Open Access

  Differential regulation of β-catenin-mediated transcription via N- and C-terminal co-factors governs identity of murine intestinal epithelial stem cells

  How downstream regulators of Wnt/β-catenin signalling control the fate of intestinal epithelial stem cells (IESCs) is unclear. Here, the authors show that the transcriptional co-factors interacting with the N- and C-terminal domains of β-catenin differentially regulate Wnt target gene activation, in turn differentially affecting the murine IESC proliferation and differentiation.

  • Costanza Borrelli
  • , Tomas Valenta
  •  & Konrad Basler

• Article
  11 January 2021 | Open Access

  CREPT is required for murine stem cell maintenance during intestinal regeneration

  The role of CREPT, a recently identified tumor-promoting gene, outside of tumors is unclear. Here, the authors identify CREPT as maintaining murine intestinal stem cells, with embryonic deletion causing impaired cell proliferation and regeneration.

  • Liu Yang
  • , Haiyan Yang
  •  & Zhijie Chang

• Article
  11 January 2021 | Open Access

  Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

  Although ulcerative colitis (UC) is a major type of inflammatory bowel disease, attempts to model it fully have fallen short. Here the authors use patient-derived iPS cells to develop a UC organoid model that recapitulates disease histological and functional features, and confirm the role of CXCL8/CXCR1 in pathogenesis.

  • Samaneh K. Sarvestani
  • , Steven Signs
  •  & Emina H. Huang

• Perspective
  07 December 2020 | 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

• Article
  23 October 2020 | Open Access

  Prime editing for functional repair in patient-derived disease models

  Prime editing uses Cas9 nickase fused to a reverse transcriptase to edit genetic information. Here, the authors prime edit primary adult stem cells in 3D organoid cultures to show functional correction of pathogenic mutations without genome-wide off-target effects.

  • Imre F. Schene
  • , Indi P. Joore
  •  & Sabine A. Fuchs

• Article
  22 May 2020 | Open Access

  TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating microbiome-induced Akt signaling

  The molecular mechanisms that regulate intestinal Clu+ revival stem cells (revSCs) and their niche to enable regeneration in response to injury are unclear. Here, the authors show that mice without the phospholipid transport protein, TNFAIP8, causes less revSCs to be induced following injury.

  • Jason R. Goldsmith
  • , Nina Spitofsky
  •  & Youhai H. Chen

• Article
  22 April 2020 | Open Access

  Lgr5+ telocytes are a signaling source at the intestinal villus tip

  Epithelial gene expression has been shown to be zonated along the crypt-villus axis, but mechanisms shaping this spatial variability were unknown. Here, Bahar Halpern et al. uncover zonation of mesenchymal cells, including Lgr5+ telocytes, which regulate epithelial gene expression at the villus tip.

  • Keren Bahar Halpern
  • , Hassan Massalha
  •  & Shalev Itzkovitz

• Article
  24 January 2020 | Open Access

  Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration

  Gut microbiota and their metabolites regulate homeostasis of the intestine, but their effects on intestine development are unclear. Here the authors use RNAseq and germ free mice to show that intestinal microbiota promote the expression of Erdr1, which increases Lgr5⁺ intestinal stem cell number and activity.

  • Hirohito Abo
  • , Benoit Chassaing
  •  & Timothy L. Denning

• Article
  08 January 2020 | Open Access

  Prox1-positive cells monitor and sustain the murine intestinal epithelial cholinergic niche

  Acetylcholine regulates intestinal epithelial secretion via muscarinic Gq-coupled receptors but its role in cell differentiation is unclear. Here, the authors show that Prox1-positive endocrine cells are sensors for the cholinergic intestinal niche and can trigger increased differentiation of enteroendocrine DCLK1-positive tuft cells.

  • Moritz Middelhoff
  • , Henrik Nienhüser
  •  & Timothy C. Wang

• Article
  11 December 2019 | Open Access

  Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

  Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.

  • Giovanni Giuseppe Giobbe
  • , Claire Crowley
  •  & Paolo De Coppi

• Article
  25 September 2019 | Open Access

  R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon

  Epithelial turnover in the colon requires stem cells in the crypt that express the R-spondin receptor Lgr5. Here, the authors show that regeneration after colon injury involving loss of Lgr5⁺ and Axin2⁺ cells requires stromal derived Rspo3-dependent reprogramming of Lgr4⁺ differentiated cells, including Krt20⁺ enterocytes.

  • Christine Harnack
  • , Hilmar Berger
  •  & Michael Sigal

• Article
  25 September 2019 | Open Access

  Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut

  Epithelia are exposed to diverse types of environmental stress, but the mechanisms by which epithelial cells sense stress are not well understood. Here, the authors show that a Nox-ROS-Ask1-MKK3-p38 signaling axis integrates various types of stress to promote intestinal regeneration.

  • Parthive H. Patel
  • , Clothilde Pénalva
  •  & Bruce A. Edgar

• Article
  11 September 2019 | Open Access

  The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine

  Notch signaling mediates intestinal enteroblast specification in Drosophila but the molecular mechanism as to how this is regulated is unclear. Here, the authors show that the transcription factor Klumpfuss ensures enteroblast commitment through repression of enteroendocrine cell fate downstream of Notch.

  • Jerome Korzelius
  • , Sina Azami
  •  & Heinrich Jasper

• Article
  05 July 2019 | Open Access

  AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis

  Regeneration after injury in the Drosophila intestine involves early activation of intestinal stem cells (ISCs) and subsequent return to quiescence. Here the authors show that return to quiescence by ISCs involves BMP Type I receptor Tkv protein stabilization along with AWD mediated internalization into endocytic vesicles.

  • Xiaoyu Tracy Cai
  • , Hongjie Li
  •  & Heinrich Jasper

• Article
  23 April 2019 | Open Access

  The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis

  The histone variant, H2A.Z is known to regulate gene expression and cell proliferation. Here the authors show that H2A.Z has a central role in the control of intestinal epithelial homeostasis in mice, by preventing terminal differentiation of intestinal progenitors.

  • Jérémie Rispal
  • , Lucie Baron
  •  & Fabrice Escaffit

• Article
  15 April 2019 | Open Access

  Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling

  Early life stress has been associated with the occurrence of gastrointestinal diseases later in life, but underlying mechanisms remain poorly understood. Here, Wong et al. show that early life stress leads to expansion of intestinal stem cells and their differentiation into serotonin-producing enterochromaffin cells through crosstalk between NGF and Wnt signalling pathways.

  • Hoi Leong Xavier Wong
  • , Hong-yan Qin
  •  & Zhao-xiang Bian

• Article
  06 March 2019 | Open Access

  Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation

  Lgr5+ stem cells in intestinal crypts are critical for gut epithelium homeostasis. Here, the authors show that Znht1 critically regulates intestinal homeostasis by promoting interaction between histone variant H2A.Z and its chaperone YL1 to incorporate H2A.Z into genes involved in intestinal stem cell fate.

  • Bing Zhao
  • , Ying Chen
  •  & Xinhua Lin

• Article
  05 March 2019 | Open Access

  Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction

  Protein homeostasis maintenance (proteostasis) is critical for cell function, but declines during aging. Here the authors detail a proteostatic checkpoint in Drosophila intestinal stem cells coordinating cell cycle arrest with protein aggregate clearance, along with its role in aging related intestinal dysfunction.

  • Imilce A. Rodriguez-Fernandez
  • , Yanyan Qi
  •  & Heinrich Jasper

• Article
  13 February 2019 | Open Access

  Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer

  Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

  • David M. Gay
  • , Rachel A. Ridgway
  •  & Owen J. Sansom

• Article
  21 January 2019 | Open Access

  Anti-LRP5/6 VHHs promote differentiation of Wnt-hypersensitive intestinal stem cells

  Enhanced Wnt receptor activity is a major cause of cancer development. Here the authors identify camelid single-domain antibody fragments (VHHs) that bind to the Wnt receptor LRP5/6 ectodomain, determine the crystal structures and show that these VHHs selectively inhibit Wnt3- mediated cellular responses and block the growth of mutant Wnt-hypersensitive intestinal tumor organoids.

  • Nicola Fenderico
  • , Revina C. van Scherpenzeel
  •  & Madelon M. Maurice