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https://www.readbyqxmd.com/read/28736217/high-content-screening-in-hpsc-neural-progenitors-identifies-drug-candidates-that-inhibit-zika-virus-infection-in-fetal-like-organoids-and-adult-brain
#1
Ting Zhou, Lei Tan, Gustav Y Cederquist, Yujie Fan, Brigham J Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J Brennand, Qisheng Zhang, Robert E Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids...
July 19, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28717211/epithelial-cell-specific-raptor-is-required-for-initiation-of-type-2-mucosal-immunity-in-small-intestine
#2
Bola Aladegbami, Lauren Barron, James Bao, Jason Colasanti, Christopher R Erwin, Brad W Warner, Jun Guo
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638807/translational-rodent-models-for-research-on-parasitic-protozoa-a-review-of-confounders-and-possibilities
#3
REVIEW
Totta Ehret, Francesca Torelli, Christian Klotz, Amy B Pedersen, Frank Seeber
Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28614372/intestinal-organoids-model-human-responses-to-infection-by-commensal-and-shiga-toxin-producing-escherichia-coli
#4
Sayali S Karve, Suman Pradhan, Doyle V Ward, Alison A Weiss
Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28534760/minibrain-storm-cerebral-organoids-aren-t-real-brains-but-they-provide-a-powerful-platform-for-modeling-brain-diseases-like-zika-infection-alzheimer-s-and-even-autism
#5
Shannon Fischer
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#6
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
May 10, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28484457/type-i-and-type-iii-interferons-display-different-dependency-on-mitogen-activated-protein-kinases-to-mount-an-antiviral-state-in-the-human-gut
#7
Kalliopi Pervolaraki, Megan L Stanifer, Stephanie Münchau, Lynnsey A Renn, Dorothee Albrecht, Stefan Kurzhals, Elena Senís, Dirk Grimm, Jutta Schröder-Braunstein, Ronald L Rabin, Steeve Boulant
Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28475412/pi3k-akt-mtor-axis-sustains-rotavirus-infection-via-the-4e-bp1-mediated-autophagy-pathway-and-represents-an-antiviral-target
#8
Yuebang Yin, Wen Dang, Xinying Zhou, Lei Xu, Wenshi Wang, Wanlu Cao, Sunrui Chen, Junhong Su, Xuepeng Cai, Shaobo Xiao, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies...
May 5, 2017: Virulence
https://www.readbyqxmd.com/read/28469201/flagellar-hooks-and-hook-protein-flge-participate-in-host-microbe-interactions-at-immunological-level
#9
Ying Shen, Lin Chen, Meixiang Wang, Dandan Lin, Zhongjie Liang, Peiqing Song, Qing Yuan, Hua Tang, Weihua Li, Kangmin Duan, Baiyan Liu, Ge Zhao, Yiqiang Wang
Host-microbe interactions determine the outcome of host responses to commensal and pathogenic microbes. Previously, two epithelial cell-binding peptides were found to be homologues of two sites (B, aa168-174; F, aa303-309) in the flagellar hook protein FlgE of Pseudomonas aeruginosa. Tertiary modeling predicted these sites at the interface of neighboring FlgE monomers in the fully formed hook. Recombinant FlgE protein stimulated proinflammatory cytokine production in a human cell line and in murine lung organoid culture as detected with real-time RT-PCR and ELISA assays...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448600/mscs-feeder-layers-induce-smg-self-organization-and-branching-morphogenesis
#10
Mahmoud Farahat, Gulsan Ara Sathi, Emilio Satoshi Hara, Hiroaki Taketa, Takuo Kuboki, Takuya Matsumoto
Dysfunction of salivary glands leads to several oral health problems, including dental caries, mastication and swallowing dysfunctions and multiple oral infections. Conventional treatments for such condition fell short of providing satisfying therapeutic results. Recent advances in organ regeneration therapy which utilize tissue stem cells to fabricate bioengineered 3D organ buds, have introduced a promising therapeutic tool for full functional organ regeneration. However, finding a sustainable and easily accessible cell source for such approaches is still challenging, especially in case of severely atrophied tissues such as irradiated salivary glands...
2017: PloS One
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#11
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#12
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#13
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346922/epigenetics-in-gastrointestinal-health-and-disease-spotlight-on-dna-methylation-in-the-intestinal-epithelium
#14
Matthias Zilbauer, Judith Kraiczy
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations...
2017: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/28314593/25-hydroxycholesterol-protects-host-against-zika-virus-infection-and-its-associated-microcephaly-in-a-mouse-model
#15
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28151409/helicobacter-pylori-induced-gastric-pathology-insights-from-in-vivo-and-ex-vivo-models
#16
REVIEW
Michael D Burkitt, Carrie A Duckworth, Jonathan M Williams, D Mark Pritchard
Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H...
February 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28132835/recent-zika-virus-isolates-induce-premature-differentiation-of-neural-progenitors-in-human-brain-organoids
#17
Elke Gabriel, Anand Ramani, Ulrike Karow, Marco Gottardo, Karthick Natarajan, Li Ming Gooi, Gladiola Goranci-Buzhala, Oleg Krut, Franziska Peters, Milos Nikolic, Suvi Kuivanen, Essi Korhonen, Teemu Smura, Olli Vapalahti, Argyris Papantonis, Jonas Schmidt-Chanasit, Maria Riparbelli, Giuliano Callaini, Martin Krönke, Olaf Utermöhlen, Jay Gopalakrishnan
The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28124153/gastric-organoids-an-emerging-model-system-to-study-helicobacter-pylori-pathogenesis
#18
REVIEW
Malvika Pompaiah, Sina Bartfeld
Helicobacter research classically uses fixed human tissue, animal models or cancer cell lines. Each of these study objects has its advantages and has brought central insights into the infection process. Nevertheless, in model systems for basic and medical research, there is a gap between two-dimensional and most often transformed cell cultures and three-dimensional, highly organized tissues. In recent years, stem cell research has provided the means to fill this gap. The identification of the niche factors that support growth, expansion and differentiation of stem cells in vitro has allowed the development of three-dimensional culture systems called organoids...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28041895/induction-of-expansion-and-folding-in-human-cerebral-organoids
#19
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...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28005068/immuno-engineered-organoids-for-regulating-the-kinetics-of-b-cell-development-and-antibody-production
#20
Alberto Purwada, Ankur Singh
Induction of B-cell immunity against infection depends on the initiation of the germinal center (GC) reaction in secondary lymphoid organs. Ex vivo recapitulation of the GC reaction in 2D cultures results in transient cell growth, with poor yield and short-term survival. Furthermore, no reported 2D ex vivo system can modulate the kinetics of a GC-like phenotype or the rate of antibody class switching. This protocol describes a methodology for developing immune organoids that partially mimic the B-cell zone of a lymphoid tissue, for efficient and rapid generation of B cells with a GC-like phenotype from naive murine B cells...
January 2017: Nature Protocols
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