22 Result(s)
within
Marc van de Wetering
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Article
Open AccessAtypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities
Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or
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Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors
Patient-derived organoids (PDOs) recapitulate tumor architecture, contain cancer stem cells and have predictive value supporting personalized medicine. Here we describe a large-scale functional screen of dual-...
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Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids
Chromosome segregation errors cause aneuploidy and genomic heterogeneity, which are hallmarks of cancer in humans. A persistent high frequency of these errors (chromosomal instability (CIN)) is predicted to pr...
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Intra-tumour diversification in colorectal cancer at the single-cell level
Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and ...
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Open AccessFANTOM5 CAGE profiles of human and mouse samples
In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expres...
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Tissue-specific mutation accumulation in human adult stem cells during life
Stem cells of the liver, colon and small intestine gradually accumulate mutations throughout life at a similar rate even though cancer incidence varies greatly among these tissues.
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Sequential cancer mutations in cultured human intestinal stem cells
Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal gr...
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Open AccessTransformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2
The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach a...
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Genome sequencing of normal cells reveals developmental lineages and mutational processes
On the basis of whole-genome sequences of clonal lines derived from normal mouse tissues, variation in mutational patterns and load across different tissues are described and early embryonic cell divisions are...
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Open AccessDNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus
DNA methylation is of pivotal importance during development. Previous genome-wide studies identified numerous differentially methylated regions upon differentiation of stem cells, many of them associated with ...
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Article
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
A mouse model of liver damage has identified a population of Lrg5+ liver stem cells that can generate hepatoctyes and bile ducts in vivo.
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Dll1+ secretory progenitor cells revert to stem cells upon crypt damage
Notch signalling in the intestinal crypt is modulated to drive commitment to the secretory fate. Clevers and colleagues find that cells expressing the Notch ligand DLL1 are intermediate secretory cells that ca...
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Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors
In vivo and in vitro studies show that the stem-cell E3 ubiquitin ligases RNF43 and ZNRF3 act as tumour suppressors in colorectal cancer models, and are involved in the negative regulation of the cancer-associate...
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Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling
Lrig1, a transmembrane glycoprotein, has previously been shown to inhibit ErbB signalling. Jensen and colleagues show that Lrig1 controls the size of the intestinal stem-cell niche by modulating the amplitude ...
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Single-cell dissection of transcriptional heterogeneity in human colon tumors
Not all cells in a tumor are alike, but our ability to characterize cancer heterogeneity in detail has been limited. Dalerba et al. use high-throughput single-cell expression analysis to define clinically relevan...
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Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene e...
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Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Paneth cells, specialized cells found in the intestinal epithelium, are known to protect stem cells by producing bactericidal compounds. Now another crucial function is reported: they provide the essential nic...
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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 c...
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Crypt stem cells as the cells-of-origin of intestinal cancer
Inappropriate activation of the Wnt signalling pathway in intestinal stem cells causes them to become cancerous. Two papers in this issue help identify the cell type at the root of this cancer, which should in...
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Article
The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors
Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/β-catenin as a transcriptional co-activator1,2,3,4,5,6,7. However, studies of Drosophila, Xenopus and Caenorhabd...
