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https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#1
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28079116/katanin-p80-numa-and-cytoplasmic-dynein-cooperate-to-control-microtubule-dynamics
#2
Mingyue Jin, Oz Pomp, Tomoyasu Shinoda, Shiori Toba, Takayuki Torisawa, Ken'ya Furuta, Kazuhiro Oiwa, Takuo Yasunaga, Daiju Kitagawa, Shigeru Matsumura, Takaki Miyata, Thong Teck Tan, Bruno Reversade, Shinji Hirotsune
Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078320/lgr4-and-lgr5-function-redundantly-during-human-endoderm-differentiation
#3
Yu-Hwai Tsai, David R Hill, Namit Kumar, Sha Huang, Alana M Chin, Briana R Dye, Melinda S Nagy, Michael P Verzi, Jason R Spence
BACKGROUND & AIMS: The Lgr family of transmembrane proteins (Lgr4, 5, 6) act as functional receptors for R-spondin proteins (Rspo 1, 2, 3, 4), and potentiate Wnt signaling in different contexts. Lgr5 is arguably the best characterized of the Lgr family members in a number of adult and embryonic contexts in mice. However, the function of LGR family members in early embryonic development is unclear, and has not been explored during human development or tissue differentiation in detail. METHODS: We interrogated the function and expression of LGR family members using human pluripotent stem cell-derived tissues including definitive endoderm, mid/hindgut, and intestinal organoids...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28074039/cd34-mesenchymal-cells-are-a-major-component-of-the-intestinal-stem-cells-niche-at-homeostasis-and-after-injury
#4
Igor Stzepourginski, Giulia Nigro, Jean-Marie Jacob, Sophie Dulauroy, Philippe J Sansonetti, Gérard Eberl, Lucie Peduto
The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28072391/braf-v600e-cooperates-with-cdx2-inactivation-to-promote-serrated-colorectal-tumorigenesis
#5
Naoya Sakamoto, Ying Feng, Carmine Stolfi, Yuki Kurosu, Maranne Green, Jeffry Lin, Megan Green, Kazuhiro Sentani, Wataru Yasui, Martin McMahon, Karin M Hardiman, Jason R Spence, Nobukatsu Horita, Joel K Greenson, Rork Kuick, Kathy R Cho, Eric R Fearon
While 20-30% of colorectal cancers (CRCs) may arise from precursors with serrated glands, only 8-10% of CRCs manifest serrated morphology at diagnosis. Markers for distinguishing CRCs arising from 'serrated' versus 'conventional adenoma' precursors are lacking. We studied 36 human serrated CRCs and found CDX2 loss or BRAF mutations in ~60% of cases and often together (p= .04). CDX2(Null)/BRAF(V600E) expression in adult mouse intestinal epithelium led to serrated morphology tumors (including carcinomas) and BRAF(V600E) potently interacted with CDX2 silencing to alter gene expression...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28064442/tumor-derived-spheroids-relevance-to-cancer-stem-cells-and-clinical-applications
#6
REVIEW
Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto
Recently, many types of in vitro three-dimensional (3D) culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3D culture methods aim to preserve the biological characteristics of original tumors better than conventional two-dimensional (2D) monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28063930/systematic-time-dependent-visualization-and-quantitation-of-the-neurogenic-rate-in-brain-organoids
#7
Yoichi Kosodo, Taeko Suetsugu, Tetsuya J Kobayashi, Fumio Matsuzaki
Organoids mimicking the formation of the brain cortex have been demonstrated to be powerful tools for developmental studies as well as pathological investigations of brain malformations. Here, we report an integrated approach for the quantification of temporal neural production (neurogenic rate) in organoids derived from embryonic brains. Spherical tissue fragments with polarized cytoarchitectures were incubated in multiple cavities arranged in a polymethylmethacrylate chip. The time-dependent neurogenic rate in the organoids was monitored by the level of EGFP under the promoter of Tbr2, a transcription factor that is transiently expressed in neural fate-committed progenitors during corticogenesis...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28061355/hacking-the-matrix
#8
Michael Czerwinski, Jason R Spence
Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28061353/created-of-warm-blood-and-nerves-restoring-an-enteric-nervous-system-in-organoids
#9
Christopher R Schlieve, Tracy C Grikscheit
The enteric nervous system (ENS) regulates numerous gastrointestinal functions, including epithelial barrier permeability and motility. In a recent Nature Medicine study, Workman et al. (2016) propose a method for introducing human pluripotent stem cell-derived enteric neural crest cells into developing human intestinal organoids, thereby restoring ENS cell types and contractile function.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#10
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28052255/personalized-proteome-profiles-of-healthy-and-tumor-human-colon-organoids-reveal-both-individual-diversity-and-basic-features-of-colorectal-cancer
#11
Alba Cristobal, Henk W P van den Toorn, Marc van de Wetering, Hans Clevers, Albert J R Heck, Shabaz Mohammed
Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052057/wnt-%C3%AE-catenin-promotes-gastric-fundus-specification-in-mice-and-humans
#12
Kyle W McCracken, Eitaro Aihara, Baptiste Martin, Calyn M Crawford, Taylor Broda, Julie Treguier, Xinghao Zhang, John M Shannon, Marshall H Montrose, James M Wells
Despite the global prevalence of gastric disease, there are few adequate models in which to study the fundus epithelium of the human stomach. We differentiated human pluripotent stem cells (hPSCs) into gastric organoids containing fundic epithelium by first identifying and then recapitulating key events in embryonic fundus development. We found that disruption of Wnt/β-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that β-catenin activation in hPSC-derived foregut progenitors promoted the development of human fundic-type gastric organoids (hFGOs)...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28045944/pharmaceutical-metabolism-in-fish-using-a-3-d-hepatic-in-vitro-model-to-assess-clearance
#13
Matthew G Baron, Kate S Mintram, Stewart F Owen, Malcolm J Hetheridge, A John Moody, Wendy M Purcell, Simon K Jackson, Awadhesh N Jha
At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay...
2017: PloS One
https://www.readbyqxmd.com/read/28044412/adult-gastric-stem-cells-and-their-niches
#14
REVIEW
Sina Bartfeld, Bon-Kyoung Koo
Adult gastric stem cells replenish the gastric epithelium throughout life. Recent studies have identified diverse populations of stem cells, progenitor cells, and even differentiated cells that can regain stem cell capacity, so highlighting an unexpected plasticity within the gastric epithelium, both in the corpus and antrum. Two niches seem to co-exist in the gastric unit: one in the isthmus region and the other at the base of the gland, although the precise features of the cell populations and the two niches are currently under debate...
January 3, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28043965/cell-scientist-to-watch-madeline-lancaster
#15
(no author information available yet)
Madeline Lancaster received her first degree in biochemistry from the Occidental College in Los Angeles, California, and continued to follow her interests by pursuing a PhD in biomedical sciences in the laboratory of Joseph Gleeson at University of California, San Diego. She then left the USA to train as a postdoctoral fellow with Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna. Madeline was a recipient of the EMBO, Helen Hay Whitney and Marie Curie Incoming Fellowships, and in 2014 her work was recognised when she was awarded the Eppendorf Award for Young Investigators...
January 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28041895/induction-of-expansion-and-folding-in-human-cerebral-organoids
#16
Yun Li, Julien Muffat, Attya Omer, Irene Bosch, Madeline A Lancaster, Mriganka Sur, Lee Gehrke, Juergen A Knoblich, Rudolf Jaenisch
An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids...
December 20, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28031422/organoids-a-historical-perspective-of-thinking-in-three-dimensions
#17
REVIEW
Marina Simian, Mina J Bissell
In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. However, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? Here, we summarize how work over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28017905/stem-cell-derived-kidney-cells-and-organoids-recent-breakthroughs-and-emerging-applications
#18
REVIEW
Jacqueline Kai Chin Chuah, Daniele Zink
The global rise in the numbers of kidney patients and the shortage in transplantable organs have led to an increasing interest in kidney-specific regenerative therapies, renal disease modelling and bioartificial kidneys. Sources for large quantities of high-quality renal cells and tissues would be required, also for applications in in vitro platforms for compound safety and efficacy screening. Stem cell-based approaches for the generation of renal-like cells and tissues would be most attractive, but such methods were not available until recently...
December 23, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/28017656/primary-human-testicular-cells-self-organize-into-organoids-with-testicular-properties
#19
Yoni Baert, Joery De Kock, João P Alves-Lopes, Olle Söder, Jan-Bernd Stukenborg, Ellen Goossens
So far, successful de novo formation of testicular tissue followed by complete spermatogenesis in vitro has been achieved only in rodents. Our findings reveal that primary human testicular cells are able to self-organize into human testicular organoids (TOs), i.e., multi-cellular tissue surrogates, either with or without support of a biological scaffold. Despite lacking testis-specific topography, these mini-tissues harbored spermatogonia and their important niche cells, which retained specific functionalities during long-term culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28009303/cerebral-organoids-recapitulate-epigenomic-signatures-of-the-human-fetal-brain
#20
Chongyuan Luo, Madeline A Lancaster, Rosa Castanon, Joseph R Nery, Juergen A Knoblich, Joseph R Ecker
Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains...
December 20, 2016: Cell Reports
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