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https://www.readbyqxmd.com/read/29241552/a-single-cell-rna-sequencing-study-reveals-cellular-and-molecular-dynamics-of-the-hippocampal-neurogenic-niche
#1
Benedetta Artegiani, Anna Lyubimova, Mauro Muraro, Johan H van Es, Alexander van Oudenaarden, Hans Clevers
Adult neurogenesis in the murine dentate gyrus occurs in a specialized microenvironment that sustains the generation of neurons during life. To fully understand adult neurogenesis, it is essential to determine the neural stem cell (NSC) and progenitor developmental stages, their molecular determinants, and the niche cellular and molecular composition. We report on a single-cell RNA sequencing study of the hippocampal niche, performed by isolating all the non-neuronal cell populations. Our analysis provides a comprehensive description of the dentate gyrus cells, and it allows the identification of exclusive cell-type-specific markers...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29237753/troy-tnfrsf19-marks-epithelial-progenitor-cells-during-mouse-kidney-development-that-continue-to-contribute-to-turnover-in-adult-kidney
#2
Frans Schutgens, Maarten B Rookmaaker, Francis Blokzijl, Ruben van Boxtel, Robert Vries, Edwin Cuppen, Marianne C Verhaar, Hans Clevers
During kidney development, progressively committed progenitor cells give rise to the distinct segments of the nephron, the functional unit of the kidney. Similar segment-committed progenitor cells are thought to be involved in the homeostasis of adult kidney. However, markers for most segment-committed progenitor cells remain to be identified. Here, we evaluate Troy/TNFRSF19 as a segment-committed nephron progenitor cell marker. Troy is expressed in the ureteric bud during embryonic development. During postnatal nephrogenesis, Troy+ cells are present in the cortex and papilla and display an immature tubular phenotype...
December 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29224780/a-living-biobank-of-breast-cancer-organoids-captures-disease-heterogeneity
#3
Norman Sachs, Joep de Ligt, Oded Kopper, Ewa Gogola, Gergana Bounova, Fleur Weeber, Anjali Vanita Balgobind, Karin Wind, Ana Gracanin, Harry Begthel, Jeroen Korving, Ruben van Boxtel, Alexandra Alves Duarte, Daphne Lelieveld, Arne van Hoeck, Robert Frans Ernst, Francis Blokzijl, Isaac Johannes Nijman, Marlous Hoogstraat, Marieke van de Ven, David Anthony Egan, Vittoria Zinzalla, Jurgen Moll, Sylvia Fernandez Boj, Emile Eugene Voest, Lodewyk Wessels, Paul Joannes van Diest, Sven Rottenberg, Robert Gerhardus Jacob Vries, Edwin Cuppen, Hans Clevers
Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging...
December 5, 2017: Cell
https://www.readbyqxmd.com/read/29215633/measuring-mutation-accumulation-in-single-human-adult-stem-cells-by-whole-genome-sequencing-of-organoid-cultures
#4
Myrthe Jager, Francis Blokzijl, Valentina Sasselli, Sander Boymans, Roel Janssen, Nicolle Besselink, Hans Clevers, Ruben van Boxtel, Edwin Cuppen
Characterization of mutational processes in adult stem cells (ASCs) will improve our understanding of aging-related diseases, such as cancer and organ failure, and may ultimately help prevent the development of these diseases. Here, we present a method for cataloging mutations in individual human ASCs without the necessity of using error-prone whole-genome amplification. Single ASCs are expanded in vitro into clonal organoid cultures to generate sufficient DNA for accurate whole-genome sequencing (WGS) analysis...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29212806/syndecan-1-promotes-wnt-%C3%AE-catenin-signaling-in-multiple-myeloma-by-presenting-wnts-and-r-spondins
#5
Zemin Ren, Harmen van Andel, Wim de Lau, Robin B Hartholt, Madelon M Maurice, Hans Clevers, Marie José Kersten, Marcel Spaargaren, Steven T Pals
Multiple myeloma (MM) is characterized by the expansion of malignant plasma cells in the bone marrow (BM). Most MMs display aberrant Wnt/β-catenin signaling, which drives proliferation; however, they lack oncogenic Wnt-pathway mutations, suggesting activation by autocrine Wnt ligands and/or paracrine Wnts from the BM microenvironment. Expression of the heparan sulfate proteoglycan (HSPG) syndecan-1 is a hallmark of MM. Syndecan-1 is a critical player in the complex reciprocal interaction between MM cells and their BM niche, mediating growth factor/cytokine binding and signaling by its heparan sulfate (HS) chains...
December 6, 2017: Blood
https://www.readbyqxmd.com/read/29206104/science-forum-the-human-cell-atlas
#6
Aviv Regev, Sarah A Teichmann, Eric S Lander, Ido Amit, Christophe Benoist, Ewan Birney, Bernd Bodenmiller, Peter J Campbell, Piero Carninci, Menna Clatworthy, Hans Clevers, Bart Deplancke, Ian Dunham, James Eberwine, Roland Eils, Wolfgang Enard, Andrew Farmer, Lars Fugger, Berthold Göttgens, Nir Hacohen, Muzlifah Haniffa, Martin Hemberg, Seung K Kim, Paul Klenerman, Arnold Kriegstein, Ed Lein, Sten Linnarsson, Emma Lundberg, Joakim Lundeberg, Partha Majumder, John C Marioni, Miriam Merad, Musa Mhlanga, Martijn Nawijn, Mihai Netea, Garry Nolan, Dana Pe'er, Anthony Phillipakis, Chris P Ponting, Stephen R Quake, Wolf Reik, Orit Rozenblatt-Rosen, Joshua R Sanes, Rahul Satija, Ton N Schumacher, Alex K Shalek, Ehud Shapiro, Padmanee Sharma, Jay W Shin, Oliver Stegle, Michael R Stratton, Michael J T Stubbington, Fabian J Theis, Matthias Uhlen, Alexander van Oudenaarden, Allon Wagner, Fiona M Watt, Jonathan S Weissman, Barbara J Wold, Ramnik J Xavier, Nir Yosef
The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology)...
December 5, 2017: ELife
https://www.readbyqxmd.com/read/29162437/mouse-model-of-alagille-syndrome-and-mechanisms-of-jagged1-missense-mutations
#7
Emma R Andersson, Indira V Chivukula, Simona Hankeova, Marika Sjöqvist, Yat Long Tsoi, Daniel Ramsköld, Jan Masek, Aiman Elmansuri, Anita Hoogendoorn, Elenae Vazquez, Helena Storvall, Julie Netušilová, Meritxell Huch, Björn Fischler, Ewa Ellis, Adriana Contreras, Antal Nemeth, Kenneth C Chien, Hans Clevers, Rickard Sandberg, Vitezslav Bryja, Urban Lendahl
BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms. METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1(+)/(Ndr) mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1(Ndr/Ndr) mice)...
November 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29117169/corrigendum-genome-wide-crispr-screens-reveal-a-wnt-fzd5-signaling-circuit-as-a-druggable-vulnerability-of-rnf43-mutant-pancreatic-tumors
#8
Zachary Steinhart, Zvezdan Pavlovic, Megha Chandrashekhar, Traver Hart, Xiaowei Wang, Xiaoyu Zhang, Mélanie Robitaille, Kevin R Brown, Sridevi Jaksani, René Overmeer, Sylvia F Boj, Jarrett Adams, James Pan, Hans Clevers, Sachdev Sidhu, Jason Moffat, Stéphane Angers
This corrects the article DOI: 10.1038/nm.4219.
November 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29018034/a-distinct-cellular-basis-for-early-cardiac-arrhythmias-the-cardinal-manifestation-of-arrhythmogenic-cardiomyopathy-and-the-skin-phenotype-of-cardiocutaneous-syndromes
#9
Jennifer Karmouch, Qiong Q Zhou, Christina Y Miyake, Raffaella Lombardi, Kai Kretzschmar, Marie Bannier-Hélaouët, Hans Clevers, Xander H Wehrens, James T Willerson, Ali J Marian
Rationale: Arrhythmogenic cardiomyopathy (ACM) is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early manifestations, whereas myocardial fibroadiposis is the pathological hallmark. Homozygous DSP (desmoplakin) and JUP (plakoglobin) mutations are responsible for a subset of ACM patients that exhibit cardiac arrhythmias and dysfunction, palmo-planter keratosis, and hair abnormalities (cardiocutaneous syndromes). Objective: To determine phenotypic consequences of deletion of Dsp in a subset of cells common to the heart and skin...
October 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28985214/cancer-stem-cells-revisited
#10
REVIEW
Eduard Batlle, Hans Clevers
The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response...
October 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28912576/interrogating-open-issues-in-cancer-medicine-with-patient-derived-xenografts
#11
Annette T Byrne, Denis G Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K Chang, Robert B Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G Palmer, Daniel S Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino
This corrects the article DOI: 10.1038/nrc.2016.140.
September 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28912133/use-of-crispr-modified-human-stem-cell-organoids-to-study-the-origin-of-mutational-signatures-in-cancer
#12
Jarno Drost, Ruben van Boxtel, Francis Blokzijl, Tomohiro Mizutani, Nobuo Sasaki, Valentina Sasselli, Joep de Ligt, Sam Behjati, Judith E Grolleman, Tom van Wezel, Serena Nik-Zainal, Roland P Kuiper, Edwin Cuppen, Hans Clevers
Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology and could hold diagnostic and prognostic value. We developed a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR-Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed subcloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair-deficient colorectal cancers...
October 13, 2017: Science
https://www.readbyqxmd.com/read/28756233/organoid-culture-systems-to-study-host-pathogen-interactions
#13
REVIEW
Devanjali Dutta, Hans Clevers
Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered...
August 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#14
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor (EGF) receptor signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET coreceptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
October 2017: Gastroenterology
https://www.readbyqxmd.com/read/28714188/energy-efficient-oil-water-separation-of-biomimetic-copper-membrane-with-multiscale-hierarchical-dendritic-structures
#15
Zhiwu Han, Bo Li, Zhengzhi Mu, Shichao Niu, Junqiu Zhang, Luquan Ren
Membrane-based materials with special surface wettability have been applied widely for the treatment of increasing industrial oily waste water, as well as frequent oil spill accidents. However, traditional technologies are energy-intensive and limited, either by fouling or by the inability of a single membrane to separate all types of oil-water mixtures. Herein, a biomimetic monolayer copper membrane (BMCM), composed of multiscale hierarchical dendritic structures, is cleverly designed and successfully fabricated on steel mesh substrate...
July 17, 2017: Small
https://www.readbyqxmd.com/read/28684519/origins-of-lymphatic-and-distant-metastases-in-human-colorectal-cancer
#16
Kamila Naxerova, Johannes G Reiter, Elena Brachtel, Jochen K Lennerz, Marc van de Wetering, Andrew Rowan, Tianxi Cai, Hans Clevers, Charles Swanton, Martin A Nowak, Stephen J Elledge, Rakesh K Jain
The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees...
July 7, 2017: Science
https://www.readbyqxmd.com/read/28666112/how-the-gut-feels-smells-and-talks
#17
COMMENT
Joep Beumer, Hans Clevers
Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting enteroendocrine cells and, for the first time, demonstrate a functional synaptic interaction with neurons.
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28615312/stem-cells-in-repair-of-gastrointestinal-epithelia
#18
REVIEW
Amanda Andersson-Rolf, Matthias Zilbauer, Bon-Kyoung Koo, Hans Clevers
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity...
July 2017: Physiology
https://www.readbyqxmd.com/read/28600348/loss-of-the-wnt-receptor-frizzled-7-in-the-mouse-gastric-epithelium-is-deleterious-and-triggers-rapid-repopulation-in-vivo
#19
Dustin J Flanagan, Nick Barker, Cameron Nowell, Hans Clevers, Matthias Ernst, Toby J Phesse, Elizabeth Vincan
The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention...
August 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28575679/wnt-%C3%AE-catenin-signaling-disease-and-emerging-therapeutic-modalities
#20
REVIEW
Roel Nusse, Hans Clevers
The WNT signal transduction cascade is a main regulator of development throughout the animal kingdom. Wnts are also key drivers of most types of tissue stem cells in adult mammals. Unsurprisingly, mutated Wnt pathway components are causative to multiple growth-related pathologies and to cancer. Here, we describe the core Wnt/β-catenin signaling pathway, how it controls stem cells, and contributes to disease. Finally, we discuss strategies for Wnt-based therapies.
June 1, 2017: Cell
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