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https://www.readbyqxmd.com/read/29891677/differentiated-human-airway-organoids-to-assess-infectivity-of-emerging-influenza-virus
#1
Jie Zhou, Cun Li, Norman Sachs, Man Chun Chiu, Bosco Ho-Yin Wong, Hin Chu, Vincent Kwok-Man Poon, Dong Wang, Xiaoyu Zhao, Lei Wen, Wenjun Song, Shuofeng Yuan, Kenneth Kak-Yuen Wong, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Honglin Chen, Hans Clevers, Kwok-Yung Yuen
Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29848792/bioengineered-bile-ducts-recapitulate-key-cholangiocyte-functions
#2
Chen Chen, Paulus Jochems, Lucia Salz, Kerstin Schneeberger, Louis C Penning, Stan F J van de Graaf, Ulrich Beuers, Hans Clevers, Niels Geijsen, Rosalinde Masereeuw, Bart Spee
Investigation of diseases of the bile duct system and identification of potential therapeutic targets are hampered by the lack of tractable in vitro systems to model cholangiocyte biology. Here, we show a step-wise method for the differentiation of murine Lgr5+ liver stem cells (organoids) into cholangiocyte-like cells (CLCs) using a combination of growth factors and extracellular matrix components. Organoid-derived CLCs display key properties of primary cholangiocytes, such as expressing cholangiocyte markers, forming primary cilia, transporting small molecules and responding to farnesoid X receptor (FXR) agonist...
May 31, 2018: Biofabrication
https://www.readbyqxmd.com/read/29807351/cortical-organoids-why-all-this-hype
#3
REVIEW
Fabio Marsoner, Philipp Koch, Julia Ladewig
The development of organoids derived from human pluripotent stem cells heralded a new area in studying human organ development and pathology outside of the human body. Triggered by the seminal work of pioneers in the field such as Yoshiki Sasai or Hans Clevers, organoid research has become one of the most rapidly developing fields in cell biology. The potential applications are manifold reaching from developmental studies to tissue regeneration and drug screening. In this review, we will concentrate on brain organoids of cortical identity...
May 25, 2018: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29796608/use-and-application-of-3d-organoid-technology
#4
Benedetta Artegiani, Hans Clevers
The capacity of the 3D-organoid cultures to resemble a near-physiological tissue organization and to mimic -to a certain degree- organ functionality, make organoids an excellent model for applications spanning from basic developmental/stem cell research to personalized medicine. Here, we review key findings achieved through organoid technology and we discuss applications such as disease- and tumor modelling, correction of genetic mutations and understanding gene- and cell functions. Finally, we discuss future developments in the field...
May 23, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29773667/notch-ligand-dll1-mediates-cross-talk-between-mammary-stem-cells-and-the-macrophageal-niche
#5
Rumela Chakrabarti, Toni Celià-Terrassa, Sushil Kumar, Xiang Hang, Yong Wei, Abrar Choudhury, Julie Hwang, Jia Peng, Briana Nixon, John J Grady, Christina DeCoste, Jie Gao, Johan H van Es, Ming O Li, Iannis Aifantis, Hans Clevers, Yibin Kang
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, we show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feed back loop that promotes the function of Dll1+ MaSCs...
May 17, 2018: Science
https://www.readbyqxmd.com/read/29765026/hematopoietic-stem-cells-can-differentiate-into-restricted-myeloid-progenitors-before-cell-division-in-mice
#6
Tatyana Grinenko, Anne Eugster, Lars Thielecke, Beáta Ramasz, Anja Krüger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis, Ben Wielockx
Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29743570/enterovirus-71-infection-of-human-airway-organoids-reveals-vp1-145-as-a-viral-infectivity-determinant
#7
Sabine M G van der Sanden, Norman Sachs, Sylvie M Koekkoek, Gerrit Koen, Dasja Pajkrt, Hans Clevers, Katja C Wolthers
Human enteroviruses frequently cause severe diseases in children. Human enteroviruses are transmitted via the fecal-oral route and respiratory droplets, and primary replication occurs in the gastro-intestinal and respiratory tracts; however, how enteroviruses infect these sites is largely unknown. Human intestinal organoids have recently proven to be valuable tools for studying enterovirus-host interactions in the intestinal tract. In this study, we demonstrated the susceptibility of a newly developed human airway organoid model for enterovirus 71 (EV71) infection...
May 9, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29742387/expanding-impact-of-stem-cell-science
#8
EDITORIAL
Hans Clevers
No abstract text is available yet for this article.
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29735715/znrf3-functions-in-mammalian-sex-determination-by-inhibiting-canonical-wnt-signaling
#9
Abigail Harris, Pam Siggers, Silvia Corrochano, Nick Warr, Danielle Sagar, Daniel T Grimes, Makoto Suzuki, Rebecca D Burdine, Feng Cong, Bon-Kyoung Koo, Hans Clevers, Isabelle Stévant, Serge Nef, Sara Wells, Raja Brauner, Bochra Ben Rhouma, Neïla Belguith, Caroline Eozenou, Joelle Bignon-Topalovic, Anu Bashamboo, Ken McElreavey, Andy Greenfield
Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determination partly by opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development by inhibiting SRY-SOX9-FGF9. The molecular basis of this mutual antagonism is unclear. Here we show that ZNRF3, a WNT signaling antagonist and direct target of RSPO1-mediated inhibition, is required for sex determination in mice. XY mice lacking ZNRF3 exhibit complete or partial gonadal sex reversal, or related defects...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29692415/organoids-in-cancer-research
#10
REVIEW
Jarno Drost, Hans Clevers
The recent advances in in vitro 3D culture technologies, such as organoids, have opened new avenues for the development of novel, more physiological human cancer models. Such preclinical models are essential for more efficient translation of basic cancer research into novel treatment regimens for patients with cancer. Wild-type organoids can be grown from embryonic and adult stem cells and display self-organizing capacities, phenocopying essential aspects of the organs they are derived from. Genetic modification of organoids allows disease modelling in a setting that approaches the physiological environment...
April 24, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29643510/intra-tumour-diversification-in-colorectal-cancer-at-the-single-cell-level
#11
Sophie F Roerink, Nobuo Sasaki, Henry Lee-Six, Matthew D Young, Ludmil B Alexandrov, Sam Behjati, Thomas J Mitchell, Sebastian Grossmann, Howard Lightfoot, David A Egan, Apollo Pronk, Niels Smakman, Joost van Gorp, Elizabeth Anderson, Stephen J Gamble, Chris Alder, Marc van de Wetering, Peter J Campbell, Michael R Stratton, Hans Clevers
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 extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells...
April 2018: Nature
https://www.readbyqxmd.com/read/29593296/automated-brightfield-morphometry-of-3d-organoid-populations-by-organoseg
#12
Michael A Borten, Sameer S Bajikar, Nobuo Sasaki, Hans Clevers, Kevin A Janes
Spheroid and organoid cultures are powerful in vitro models for biology, but size and shape diversity within the culture is largely ignored. To streamline morphometric profiling, we developed OrganoSeg, an open-source software that integrates segmentation, filtering, and analysis for archived brightfield images of 3D culture. OrganoSeg is more accurate and flexible than existing platforms, and we illustrate its potential by stratifying 5167 breast-cancer spheroid and 5743 colon and colorectal-cancer organoid morphologies...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29539434/expansion-of-adult-human-pancreatic-tissue-yields-organoids-harboring-progenitor-cells-with-endocrine-differentiation-potential
#13
Cindy J M Loomans, Nerys Williams Giuliani, Jeetindra Balak, Femke Ringnalda, Léon van Gurp, Meritxell Huch, Sylvia F Boj, Toshiro Sato, Lennart Kester, Susana M Chuva de Sousa Lopes, Matthias S Roost, Susan Bonner-Weir, Marten A Engelse, Ton J Rabelink, Harry Heimberg, Robert G J Vries, Alexander van Oudenaarden, Françoise Carlotti, Hans Clevers, Eelco J P de Koning
Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi ), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29510215/factor-analysis-defines-distinct-upper-and-lower-gastrointestinal-symptom-groups-compatible-with-rome-iv-criteria-in-a-population-based-study
#14
Egbert Clevers, William E Whitehead, Olafur S Palsson, Ami D Sperber, Hans Törnblom, Lukas Van Oudenhove, Jan Tack, Magnus Simrén
BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample...
March 3, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29510214/development-of-irritable-bowel-syndrome-features-over-a-5-year-period
#15
Egbert Clevers, Jan Tack, Hans Törnblom, Gisela Ringström, Koen Luyckx, Magnus Simrén, Lukas Van Oudenhove
BACKGROUND & AIMS: There are few data from longitudinal studies of the gastrointestinal and psychologic features of irritable bowel syndrome (IBS). We studied within-person correlations among features of IBS, along with progression of gastrointestinal (GI) symptoms and quality of life, and factors associated with changes over time. METHODS: We performed a longitudinal study of 276 patients with IBS in Sweden (70% female; ages, 19-76 years) who completed questionnaires, each year for 5 years, about their GI symptom severity, quality of life, GI-specific anxiety, general anxiety, depression, and coping resources...
March 3, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29494240/defining-adult-stem-cells-by-function-not-by-phenotype
#16
Hans Clevers, Fiona M Watt
Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells...
March 1, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29311336/troy-brain-stem-cells-cycle-through-quiescence-and-regulate-their-number-by-sensing-niche-occupancy
#17
Onur Basak, Teresa G Krieger, Mauro J Muraro, Kay Wiebrands, Daniel E Stange, Javier Frias-Aldeguer, Nicolas C Rivron, Marc van de Wetering, Johan H van Es, Alexander van Oudenaarden, Benjamin D Simons, Hans Clevers
The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/ Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence...
January 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29305587/consensus-molecular-subtypes-of-colorectal-cancer-are-recapitulated-in-in-vitro-and-in-vivo-models
#18
Janneke F Linnekamp, Sander R van Hooff, Pramudita R Prasetyanti, Raju Kandimalla, Joyce Y Buikhuisen, Evelyn Fessler, Prashanthi Ramesh, Kelly A S T Lee, Grehor G W Bochove, Johan H de Jong, Kate Cameron, Ronald van Leersum, Hans M Rodermond, Marek Franitza, Peter Nürnberg, Laura R Mangiapane, Xin Wang, Hans Clevers, Louis Vermeulen, Giorgio Stassi, Jan Paul Medema
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed...
March 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29298292/imaging-organoids-a-bright-future-ahead
#19
Anne C Rios, Hans Clevers
Organogenesis, tissue homeostasis and organ function involve complex spatial cellular organization and tissue dynamics. The underlying mechanisms of these processes, and how they are disrupted in disease, are challenging to address in vivo and ethically impossible to study in human. Organoids, three-dimensional (3D) stem cell cultures that self-organize into ex vivo 'mini-organs', now open a new window onto cellular processes within tissue. Light microscopy is a powerful approach to probe the cellular complexity that can be modeled with organoids...
January 3, 2018: Nature Methods
https://www.readbyqxmd.com/read/29241552/a-single-cell-rna-sequencing-study-reveals-cellular-and-molecular-dynamics-of-the-hippocampal-neurogenic-niche
#20
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
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