Featured
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Article |
A phosphate-sensing organelle regulates phosphate and tissue homeostasis
PXo bodies, non-canonical multilamellar organelles, serve as a reservoir for intracellular inorganic phosphate and are a critical regulator of both cytosolic phosphate levels and tissue homeostasis.
- Chiwei Xu
- , Jun Xu
- & Norbert Perrimon
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Article |
Retrograde movements determine effective stem cell numbers in the intestine
Small intestinal crypts contain twice as many effective stem cells as large intestinal crypts, and this difference is determined by the degree of Wnt-driven retrograde cell movement—which is largely absent in the large intestine—counteracting conveyor-belt-like upward movement.
- Maria Azkanaz
- , Bernat Corominas-Murtra
- & Jacco van Rheenen
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Article |
Tracing oncogene-driven remodelling of the intestinal stem cell niche
By inducing changes in surrounding tissue, mutant intestinal stem cells create an unfavourable niche environment that gives them a competitive advantage over non-mutant neighbours.
- Min Kyu Yum
- , Seungmin Han
- & Benjamin D. Simons
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Article |
Apc-mutant cells act as supercompetitors in intestinal tumour initiation
Using experiments in organoids and in vivo in mice, the authors show that Apc-mutant cells act as supercompetitors to initiate the formation of adenomas.
- Sanne M. van Neerven
- , Nina E. de Groot
- & Louis Vermeulen
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Article |
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer
NOTUM from Apc-mutant cells acts as a key mediator during the early stages of mutation fixation and drives the formation of intestinal adenomas.
- Dustin J. Flanagan
- , Nalle Pentinmikko
- & Owen J. Sansom
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Article |
An organoid-based organ-repurposing approach to treat short bowel syndrome
In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.
- Shinya Sugimoto
- , Eiji Kobayashi
- & Toshiro Sato
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Article |
Phenotypic landscape of intestinal organoid regeneration
An organoid-based screening platform maps the genetic interactions underlying intestinal development and regeneration, showing that retinoic acid metabolism maintains the balance between regeneration and homeostasis, and that an antagonist of the retinoid X receptor promotes regeneration in vivo.
- Ilya Lukonin
- , Denise Serra
- & Prisca Liberali
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Article |
Homeostatic mini-intestines through scaffold-guided organoid morphogenesis
Miniature gut tubes grown in vitro from mouse intestinal stem cells are perfusable, can be colonized with microorganisms and exhibit a similar arrangement and diversity of specialized cell types to intestines in vivo.
- Mikhail Nikolaev
- , Olga Mitrofanova
- & Matthias P. Lutolf
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Article |
Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche
Single-cell RNA-sequencing analysis of intestinal mesenchyme identified a population of fibroblasts that produce prostaglandin E2, which, when disrupted, prevented initiation of intestinal tumours.
- Manolis Roulis
- , Aimilios Kaklamanos
- & Richard A. Flavell
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Article |
Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks+ island develop a distinct mutational signature associated with colorectal cancer.
- Cayetano Pleguezuelos-Manzano
- , Jens Puschhof
- & Hans Clevers
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Article |
The landscape of somatic mutation in normal colorectal epithelial cells
Genome sequencing of hundreds of normal colonic crypts from 42 individuals sheds light on mutational processes and driver mutations in normal colorectal epithelial cells.
- Henry Lee-Six
- , Sigurgeir Olafsson
- & Michael R. Stratton
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Letter |
Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium
Ageing-associated decline in intestinal stem cell function is mediated by increased Notum, a protein inhibitor of stemness-maintaining Wnt signalling, which is secreted by Paneth cells.
- Nalle Pentinmikko
- , Sharif Iqbal
- & Pekka Katajisto
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Letter |
Tracing the origin of adult intestinal stem cells
Lineage tracing, biophysical modelling and intestinal transplantation approaches are used to demonstrate that, in the mouse fetal intestinal epithelium, cells are highly plastic with respect to cellular identity and, independent of LGR5 expression and cell position, can contribute to the adult stem cell compartment.
- Jordi Guiu
- , Edouard Hannezo
- & Kim B. Jensen
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Letter |
Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell
Single-cell transcriptome profiling reveals the presence in the intestinal crypt of revival stem cells, which give rise to crypt-base columnar cells and are essential for repair of the intestinal epithelium following injury.
- Arshad Ayyaz
- , Sandeep Kumar
- & Alex Gregorieff
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Article |
Self-organization and symmetry breaking in intestinal organoid development
Single-cell-based imaging and sequencing approaches are used to characterize organoid development and the intestinal regeneration process, which is driven by transient activation of YAP1.
- Denise Serra
- , Urs Mayr
- & Prisca Liberali
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Letter |
Interleukin-22 protects intestinal stem cells against genotoxic stress
Sporadic inactivation of the interleukin-22 receptor in the intestinal epithelium of the mouse shows that IL-22 is required for effective activation of the DNA damage response following DNA damage.
- Konrad Gronke
- , Pedro P. Hernández
- & Andreas Diefenbach
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Letter |
Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche
Larvae of the parasitic helminth Heligmosomoides polygyrus induce granuloma formation and a fetal-like developmental program in granuloma-associated crypts of infected adult mice.
- Ysbrand M. Nusse
- , Adam K. Savage
- & Ophir D. Klein
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Letter |
GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells
GLI1-positive cells in the colon secrete Wnt ligands and thereby support homeostasis of intestinal stem cells.
- Bahar Degirmenci
- , Tomas Valenta
- & Konrad Basler
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Letter |
Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel
Stem cells of the Drosophila midgut sense mechanical signals in vivo through the stretch-activated ion channel Piezo, which is expressed on previously unidentified enteroendocrine precursor cells.
- Li He
- , Guangwei Si
- & Norbert Perrimon
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Letter |
Feedback regulation of steady-state epithelial turnover and organ size
Steady-state turnover of the Drosophila midgut arises through an intercellular, E-cadherin–EGFR relay that couples the death of individual enterocytes to the divisions of nearby stem cells.
- Jackson Liang
- , Shruthi Balachandra
- & Lucy Erin O’Brien
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Letter |
Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal
R-spondin and Wnt ligand families act non-redundantly and cooperatively within the same molecular pathway in the intestinal stem-cell niche to maintain stem-cell competency and drive stem-cell expansion.
- Kelley S. Yan
- , Claudia Y. Janda
- & Calvin J. Kuo
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Letter |
Designer matrices for intestinal stem cell and organoid culture
The authors have designed modular synthetic hydrogel networks for mouse and human intestinal stem cell cultures that support intestinal organoid formation.
- Nikolce Gjorevski
- , Norman Sachs
- & Matthias P. Lutolf
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Letter |
The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila
Attenuating the lipolysis pathway in Drosophila melanogaster by modulation of the COP1–Arf1 signalling complex induced necrosis in stem cells and led to their engulfment by differentiated cells.
- Shree Ram Singh
- , Xiankun Zeng
- & Steven X. Hou
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Article |
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
A high-fat diet increases the number of intestinal stem cells in mammals, both in vivo and in intestinal organoids; a pathway that involves PPAR-δ confers organoid-initiating capacity to non-stem cells and induces them to form in vivo tumours after loss of the Apc tumour suppressor.
- Semir Beyaz
- , Miyeko D. Mana
- & Ömer H. Yilmaz
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Letter |
The sexual identity of adult intestinal stem cells controls organ size and plasticity
Reversible, cell-intrinsic mechanisms that depend on a new sex differentiation pathway act in adult somatic cells of the Drosophila intestine to govern sex-specific differences in organ size, plasticity during reproduction, and response to tumorigenic insults.
- Bruno Hudry
- , Sanjay Khadayate
- & Irene Miguel-Aliaga
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Letter |
Visualization of a short-range Wnt gradient in the intestinal stem-cell niche
Generation of an epitope-tagged, functional Wnt3 knock-in allele, the signal produced by Paneth cells to regulate intestinal stem cells.
- Henner F. Farin
- , Ingrid Jordens
- & Hans Clevers
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Letter |
Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function
Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with stem-cell function.
- Elaine E. Storm
- , Steffen Durinck
- & Frederic J. de Sauvage
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Letter |
Tuft-cell-derived IL-25 regulates an intestinal ILC2–epithelial response circuit
Epithelial tuft cells are shown to be the source of intestinal interleukin (IL)-25 that is required for activation of type 2 innate lymphoid cells (ILC2s), ILC2-regulated tuft and goblet cell expansion, and control of parasite infection.
- Jakob von Moltke
- , Ming Ji
- & Richard M. Locksley
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Letter |
Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration
Innate lymphoid cells increase the growth of mouse intestinal organoids via IL-22 production; recombinant IL-22 promotes growth of both mouse and human organoids, and promotes mouse intestinal stem cell (ISC) expansion and ISC-driven organoid growth via a STAT3-dependent pathway and independently of Paneth cells; IL-22 treatment in vivo enhances the recovery of ISCs from intestinal injury.
- Caroline A. Lindemans
- , Marco Calafiore
- & Alan M. Hanash
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Article |
Signal integration by Ca2+ regulates intestinal stem-cell activity
Drosophila intestinal stem cells (ISCs) respond to changes in diet, particularly L-glutamate levels, by modulating Ca2+ signalling to adapt their proliferation rate; furthermore, Ca2+ is shown to be central to the response of ISCs to a wide range of dietary and stress stimuli.
- Hansong Deng
- , Akos A. Gerencser
- & Heinrich Jasper
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Letter |
Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer
This study finds that the Hippo pathway is essential for gut epithelial regeneration and tumour initiation; the Hippo component Yap holds off differentiation of intestinal stem cells to Paneth cells to promote a survival and self-renewal regenerative program through activation of the Egfr pathway.
- Alex Gregorieff
- , Yu Liu
- & Jeffrey L. Wrana
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Article |
Cloning and variation of ground state intestinal stem cells
Novel technology to rapidly clone patient-specific, ‘ground state’ stem cells of columnar epithelia reveals their proliferative potential, remarkably precise and origin-dependent lineage commitment as well as genomic stability, despite extensive culturing, thereby skirting limitations associated with pluripotent stem cells.
- Xia Wang
- , Yusuke Yamamoto
- & Wa Xian
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Letter |
Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging
Long-term in vivo imaging of Confetti-labelled Lgr5-expressing intestinal stem cells shows that a dynamically heterogeneous cell population is able to function long-term as an equipotent stem-cell pool.
- Laila Ritsma
- , Saskia I. J. Ellenbroek
- & Jacco van Rheenen
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Letter |
Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity
A study investigating the mechanisms underlying lateral inhibition and lineage plasticity in the mouse small intestine crypts in vivo finds that crypt cells maintain a permissive chromatin state upon which a transcription factor acts to determine lineage specification, and this is the basis of lateral inhibition.
- Tae-Hee Kim
- , Fugen Li
- & Ramesh A. Shivdasani
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Letter |
Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection
Evidence of crosstalk between the Robo/Slit and Wnt signalling pathways is provided, and R-spondin signalling is shown to enhance canonical Wnt signalling and increase the proliferation of intestinal stem cells.
- Wei-Jie Zhou
- , Zhen H. Geng
- & Jian-Guo Geng
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Article |
Intestinal label-retaining cells are secretory precursors expressing Lgr5
A new method to trace the lineage of slow cycling label-retaining cells (LRCs) in vivo identifies a population of LRCs that have features of committed Paneth cells but still express stem-cell markers such as Lgr5; the slow cycling cells differentiate into Paneth cells without cell division, but after injury can also repopulate the stem-cell niche and contribute to the regeneration of all intestinal lineages.
- Simon J. A. Buczacki
- , Heather Ireland Zecchini
- & Douglas J. Winton
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Letter |
Restriction of intestinal stem cell expansion and the regenerative response by YAP
YAP has previously been identified as an oncogene that promotes cell growth, but now it is shown to restrict stem cell expansion during regeneration in the mouse intestine, suggesting that it may function as a tumour suppressor in colon cancer.
- Evan R. Barry
- , Teppei Morikawa
- & Fernando D. Camargo
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Research Highlights |
Stem-cell genes linked to relapse
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Letter |
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
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.
- Jason R. Spence
- , Christopher N. Mayhew
- & James M. Wells
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Letter |
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Multipotent stem cells expressing Lgr5 are known to generate all cell types of the intestinal epithelium (enterocytes, goblet cells, Paneth cells and enteroendocrine cells). A new study shows that Paneth cells have an essential role for intestinal crypt and stem cell maintenance by supplying essential niche signals to the Lgr5-expressing cells.
- Toshiro Sato
- , Johan H. van Es
- & Hans Clevers
Cholinergic neurons trigger epithelial Ca2+ currents to heal the gut